Chaperone-mediated autophagy degradation of IGF-1R β induced by NVP-AUY922 in pancreatic cancer.
Chaperone-mediated autophagy degradation of IGF-1Rβ induced by NVP-AUY922 in pancreatic cancer. Cell Mol Life Sci. 2019 Apr 12;: Authors: Xue N, Lai F, Du T, Ji M, Liu D, Yan C, Zhang S, Yu X, Jin J, Chen X Abstract Enhancement of insulin-like growth factor 1 receptor (IGF-IR) degradation by heat shock protein 90 (HSP90) inhibitor is a potential antitumor therapeutic strategy. However, very little is known about how IGF-IR protein levels are degraded by HSP90 inhibitors in pancreatic cancer (PC). We found that the HSP90α inhibitor NVP-AUY922 (922) effectively downregulated and destabilized ...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Xue N, Lai F, Du T, Ji M, Liu D, Yan C, Zhang S, Yu X, Jin J, Chen X Tags: Cell Mol Life Sci Source Type: research

Regulation of WNT5A and WNT11 during MSC in vitro chondrogenesis: WNT inhibition lowers BMP and hedgehog activity, and reduces hypertrophy.
This study is the first to demonstrate that high levels of non-canonical WNT5A followed by WNT11 and LEF1 discriminated MSC chondrogenesis from AC re-differentiation. Moreover, β-catenin seemed incompletely silenced in differentiating MSCs, which altogether suggested a role for WNT signaling in hypertrophic MSC differentiation. WNT inhibition with the small molecule IWP-2 supported MSC chondrogenesis according to elevated proteoglycan deposition and reduced the characteristic upregulation of BMP4, BMP7 and their target ID1, as well as IHH and its target GLI1 observed during endochondral differentiation. Along with the...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Diederichs S, Tonnier V, März M, Dreher SI, Geisbüsch A, Richter W Tags: Cell Mol Life Sci Source Type: research

The role of the protein-RNA recognition code in neurodegeneration.
Abstract MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Research on the association between neurodegeneration and RNA-repeat toxicity provides data that support a protein-RNA recognition code. For example, this code explains why hnRNP H and SFPQ proteins, which are involved in amyotrophic lateral sclerosis...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Nahalka J Tags: Cell Mol Life Sci Source Type: research

The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining.
Abstract The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs. The Ku heterodimer has been shown to play a regulatory role in NHEJ repair. Ku80 ubiquitination contributes to the selection of a DSB repair pathway by causing the removal of Ku heterodimers from DSB sites. However, whether Ku80 deubiqu...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Li F, Sun Q, Liu K, Han H, Lin N, Cheng Z, Cai Y, Tian F, Mao Z, Tong T, Zhao W Tags: Cell Mol Life Sci Source Type: research

Adult stem cells at work: regenerating skeletal muscle.
tzahn J Abstract Skeletal muscle regeneration is a finely tuned process involving the activation of various cellular and molecular processes. Satellite cells, the stem cells of skeletal muscle, are indispensable for skeletal muscle regeneration. Their functionality is critically modulated by intrinsic signaling pathways as well as by interactions with the stem cell niche. Here, we discuss the properties of satellite cells, including heterogeneity regarding gene expression and/or their phenotypic traits and the contribution of satellite cells to skeletal muscle regeneration. We also summarize the process of regener...
Source: Cellular and Molecular Life Sciences : CMLS - April 11, 2019 Category: Cytology Authors: Schmidt M, Schüler SC, Hüttner SS, von Eyss B, von Maltzahn J Tags: Cell Mol Life Sci Source Type: research

Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a RhoD190N mutation.
Abstract D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis. Wild type (wt) and mutant rhodopsin a...
Source: Cellular and Molecular Life Sciences : CMLS - April 11, 2019 Category: Cytology Authors: Sancho-Pelluz J, Cui X, Lee W, Tsai YT, Wu WH, Justus S, Washington I, Hsu CW, Park KS, Koch S, Velez G, Bassuk AG, Mahajan VB, Lin CS, Tsang SH Tags: Cell Mol Life Sci Source Type: research

Palmitic acid is an intracellular signaling molecule involved in disease development.
Abstract Emerging evidence shows that palmitic acid (PA), a common fatty acid in the human diet, serves as a signaling molecule regulating the progression and development of many diseases at the molecular level. In this review, we focus on its regulatory roles in the development of five pathological conditions, namely, metabolic syndrome, cardiovascular diseases, cancer, neurodegenerative diseases, and inflammation. We summarize the clinical and epidemiological studies; and also the mechanistic studies which have identified the molecular targets for PA in these pathological conditions. Activation or inactivation o...
Source: Cellular and Molecular Life Sciences : CMLS - April 9, 2019 Category: Cytology Authors: Fatima S, Hu X, Gong RH, Huang C, Chen M, Wong HLX, Bian Z, Kwan HY Tags: Cell Mol Life Sci Source Type: research

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients.
In this study, we measured the expression of five circulating miRNAs (miR-195, miR-504, miR-122, miR-10b and miR-21) and evaluated their association with EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) mutation status in 66 NSCLC patients. Moreover, we examined the discriminative power of circulating miRNAs for EGFR mutant-positive and -negative NSCLC patients using two different data normalisation approaches. We extracted total RNA from the plasma of 66 non-squamous NSCLC patients (31 of whom had tumours with EGFR mutations) and measured circulating miRNA levels using quantitative reverse transcription polymerase chain reaction (...
Source: Cellular and Molecular Life Sciences : CMLS - April 5, 2019 Category: Cytology Authors: Szpechcinski A, Florczuk M, Duk K, Zdral A, Rudzinski S, Bryl M, Czyzewicz G, Rudzinski P, Kupis W, Wojda E, Giedronowicz D, Langfort R, Barinow-Wojewodzki A, Orlowski T, Chorostowska-Wynimko J Tags: Cell Mol Life Sci Source Type: research

ATAT1 regulates forebrain development and stress-induced tubulin hyperacetylation.
This study thus not only establishes the importance of ATAT1 in regulating mouse forebrain development and governing tubulin hyperacetylation during stress responses, but also suggests the existence of an additional α-tubulin acetyltransferase. PMID: 30953095 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 5, 2019 Category: Cytology Authors: Li L, Jayabal S, Ghorbani M, Legault LM, McGraw S, Watt AJ, Yang XJ Tags: Cell Mol Life Sci Source Type: research

Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering.
Abstract Plakophilins (Pkp) are desmosomal plaque proteins crucial for desmosomal adhesion and participate in the regulation of desmosomal turnover and signaling. However, direct evidence that Pkps regulate clustering and molecular binding properties of desmosomal cadherins is missing. Here, keratinocytes lacking either Pkp1 or 3 in comparison to wild type (wt) keratinocytes were characterized with regard to their desmoglein (Dsg) 1- and 3-binding properties and their capability to induce Dsg3 clustering. As revealed by atomic force microscopy (AFM), both Pkp-deficient keratinocyte cell lines showed reduced membra...
Source: Cellular and Molecular Life Sciences : CMLS - April 4, 2019 Category: Cytology Authors: Fuchs M, Foresti M, Radeva MY, Kugelmann D, Keil R, Hatzfeld M, Spindler V, Waschke J, Vielmuth F Tags: Cell Mol Life Sci Source Type: research

Role of mTORC1 in intestinal epithelial repair and tumorigenesis.
Abstract mTORC1 signaling is the prototypical pathway regulating protein synthesis and cell proliferation. mTORC1 is active in stem cells located at the base of intestinal crypts but silenced as transit-amplifying cells differentiate into enterocytes or secretory cells along the epithelium. After an insult or injury, self-limiting and controlled activation of mTORC1 is critical for the renewal and repair of intestinal epithelium. mTORC1 promotes epithelial cell renewal by driving cryptic stem cell division, and epithelial cell repair by supporting the dedifferentiation and proliferation of enterocytes or secretory...
Source: Cellular and Molecular Life Sciences : CMLS - April 3, 2019 Category: Cytology Authors: Kaur H, Moreau R Tags: Cell Mol Life Sci Source Type: research

Microglial activation in an amyotrophic lateral sclerosis-like model caused by Ranbp2 loss and nucleocytoplasmic transport impairment in retinal ganglion neurons.
Abstract Nucleocytoplasmic transport is dysregulated in sporadic and familial amyotrophic lateral sclerosis (ALS) and retinal ganglion neurons (RGNs) are purportedly involved in ALS. The Ran-binding protein 2 (Ranbp2) controls rate-limiting steps of nucleocytoplasmic transport. Mice with Ranbp2 loss in Thy1+-motoneurons develop cardinal ALS-like motor traits, but the impairments in RGNs and the degree of dysfunctional consonance between RGNs and motoneurons caused by Ranbp2 loss are unknown. This will help to understand the role of nucleocytoplasmic transport in the differential vulnerability of neuronal cell type...
Source: Cellular and Molecular Life Sciences : CMLS - April 3, 2019 Category: Cytology Authors: Cho KI, Yoon D, Yu M, Peachey NS, Ferreira PA Tags: Cell Mol Life Sci Source Type: research

AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.
Abstract To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Their trafficking to, at, and from the synapse, is, therefore, a key mechanism underlying synaptic plasticity. Intensive research over the last 20 years has revea...
Source: Cellular and Molecular Life Sciences : CMLS - April 1, 2019 Category: Cytology Authors: Bissen D, Foss F, Acker-Palmer A Tags: Cell Mol Life Sci Source Type: research

The role of ASXL1 in hematopoiesis and myeloid malignancies.
Abstract Recent high-throughput genome-wide sequencing studies have identified recurrent somatic mutations in myeloid neoplasms. An epigenetic regulator, Additional sex combs-like 1 (ASXL1), is one of the most frequently mutated genes in all subtypes of myeloid malignancies. ASXL1 mutations are also frequently detected in clonal hematopoiesis, which is associated with an increased risk of mortality. Therefore, it is important to understand how ASXL1 mutations contribute to clonal expansion and myeloid transformation in hematopoietic cells. Studies using ASXL1-depleted human hematopoietic cells and Asxl1 knockout m...
Source: Cellular and Molecular Life Sciences : CMLS - March 30, 2019 Category: Cytology Authors: Asada S, Fujino T, Goyama S, Kitamura T Tags: Cell Mol Life Sci Source Type: research

Cdc14 activation requires coordinated Cdk1-dependent phosphorylation of Net1 and PP2A-Cdc55 at anaphase onset.
alt E Abstract Exit from mitosis and completion of cytokinesis require the inactivation of mitotic cyclin-dependent kinase (Cdk) activity. In budding yeast, Cdc14 phosphatase is a key mitotic regulator that is activated in anaphase to counteract Cdk activity. In metaphase, Cdc14 is kept inactive in the nucleolus, where it is sequestered by its inhibitor, Net1. At anaphase onset, downregulation of PP2ACdc55 phosphatase by separase and Zds1 protein promotes Net1 phosphorylation and, consequently, Cdc14 release from the nucleolus. The mechanism by which PP2ACdc55 activity is downregulated during anaphase remains to b...
Source: Cellular and Molecular Life Sciences : CMLS - March 29, 2019 Category: Cytology Authors: Játiva S, Calabria I, Moyano-Rodriguez Y, Garcia P, Queralt E Tags: Cell Mol Life Sci Source Type: research

Correction to: The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.
Abstract The original version of this article unfortunately contained the following misspelling and formatting mistakes. PMID: 30919023 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - March 28, 2019 Category: Cytology Authors: Ferreira PA Tags: Cell Mol Life Sci Source Type: research

Genetics and the heart rate response to exercise.
Abstract The acute heart rate response to exercise, i.e., heart rate increase during and heart rate recovery after exercise, has often been associated with all-cause and cardiovascular mortality. The long-term response of heart rate to exercise results in favourable changes in chronotropic function, including decreased resting and submaximal heart rate as well as increased heart rate recovery. Both the acute and long-term heart rate response to exercise have been shown to be heritable. Advances in genetic analysis enable researchers to investigate this hereditary component to gain insights in possible molecular me...
Source: Cellular and Molecular Life Sciences : CMLS - March 27, 2019 Category: Cytology Authors: van de Vegte YJ, Tegegne BS, Verweij N, Snieder H, van der Harst P Tags: Cell Mol Life Sci Source Type: research

Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.
Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen. Cell Mol Life Sci. 2019 Mar 27;: Authors: Shi R, Hu W, Zhang Y, Gao S, Smith AH, Ye J, Cai L, Graham LM, Li C Abstract Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1). To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity. P4HA1 has two glycosylation sites, Asn (N) 113 and N259. Our studies show that glycosy...
Source: Cellular and Molecular Life Sciences : CMLS - March 27, 2019 Category: Cytology Authors: Shi R, Hu W, Zhang Y, Gao S, Smith AH, Ye J, Cai L, Graham LM, Li C Tags: Cell Mol Life Sci Source Type: research

Using proteomics to identify ubiquitin ligase-substrate pairs: how novel methods may unveil therapeutic targets for neurodegenerative diseases.
Abstract Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase-substrate pairs-a previously challenging feat due to the transient nature of ligase-substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiq...
Source: Cellular and Molecular Life Sciences : CMLS - March 27, 2019 Category: Cytology Authors: Rayner SL, Morsch M, Molloy MP, Shi B, Chung R, Lee A Tags: Cell Mol Life Sci Source Type: research

Inter-kingdom signaling between gut microbiota and their host.
Abstract The crosstalk between prokaryotic bacteria and eukaryotic gut epithelial cells has opened a new field for research. Quorum sensing system (QS) molecules employed by gut microbiota may play an essential role in host-microbial symbioses of the gut. Recent studies on the gut microbiome will unveil evolved mechanisms of the host to affect bacterial QS and shape bacterial composition. Bacterial autoinducers (AIs) could talk to the host's gut by eliciting proinflammatory effects and modulating the activities of T lymphocyte, macrophage, dendritic cells, and neutrophils. In addition, the gut mucosa could interfe...
Source: Cellular and Molecular Life Sciences : CMLS - March 25, 2019 Category: Cytology Authors: Li Q, Ren Y, Fu X Tags: Cell Mol Life Sci Source Type: research

The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors.
tin S Abstract Sumoylation is a reversible post-translational modification essential to the modulation of neuronal function, including neurotransmitter release and synaptic plasticity. A tightly regulated equilibrium between the sumoylation and desumoylation processes is critical to the brain function and its disruption has been associated with several neurological disorders. This sumoylation/desumoylation balance is governed by the activity of the sole SUMO-conjugating enzyme Ubc9 and a group of desumoylases called SENPs, respectively. We previously demonstrated that the activation of type 5 metabotropic glutamat...
Source: Cellular and Molecular Life Sciences : CMLS - March 23, 2019 Category: Cytology Authors: Schorova L, Pronot M, Poupon G, Prieto M, Folci A, Khayachi A, Brau F, Cassé F, Gwizdek C, Martin S Tags: Cell Mol Life Sci Source Type: research

Agonist-dependent development of delta opioid receptor tolerance in the colon.
This study examined acute and chronic tolerance to SNC80 and ARM390, which were full and partial DOR agonists in neural pathways controlling colonic motility, respectively. Excitatory pathways developed acute and chronic tolerance to SNC80, whereas only chronic tolerance developed in inhibitory pathways. Both pathways remained functional after acute or chronic ARM390 exposure. Propagating colonic motor patterns were significantly reduced after acute or chronic SNC80 treatment, but not by ARM390 pre-treatment. These findings demonstrate that SNC80 has a prolonged inhibitory effect on propagating colonic motility. ARM390 had...
Source: Cellular and Molecular Life Sciences : CMLS - March 23, 2019 Category: Cytology Authors: DiCello JJ, Saito A, Rajasekhar P, Sebastian BW, McQuade RM, Gondin AB, Veldhuis NA, Canals M, Carbone SE, Poole DP Tags: Cell Mol Life Sci Source Type: research

Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression.
Abstract Hepatitis B virus (HBV) X protein (HBx) is associated with hepatocarcinogenesis. E2-EPF ubiquitin carrier protein (UCP) catalyzes ubiquitination of itself and von Hippel-Lindau protein (pVHL) for degradation and associates with tumor growth and metastasis. However, it remains unknown whether HBx modulates the enzyme activity of UCP and thereby influences hepatocarcinogenesis. Here, we show that UCP is highly expressed in liver tissues of HBx-transgenic mice, but not non-transgenic mice. UCP was more frequently expressed in HBV-positive liver cancers than in HBV-negative liver cancers. HBx binds to UCP spe...
Source: Cellular and Molecular Life Sciences : CMLS - March 22, 2019 Category: Cytology Authors: Lim JH, Kim DG, Yu DY, Kang HM, Noh KH, Kim DS, Park D, Chang TK, Im DS, Jung CR Tags: Cell Mol Life Sci Source Type: research

A role for polycystin-1 and polycystin-2 in neural progenitor cell differentiation.
Abstract Polycystin-1 (PC1) and polycystin-2 (PC2) are transmembrane proteins encoded by the Pkd1 and Pkd2 genes, respectively. Mutations in these genes are causative for the development of autosomal-dominant polycystic kidney disease. A prominent feature of this disease is an unbalanced cell proliferation. PC1 and PC2 physically interact to form a complex, which localizes to the primary cilia of renal epithelial cells. Recently, PC1 and PC2 have also been described to be present in primary cilia of radial glial cells (RGCs) and to contribute to the planar cell polarity of late RGCs and E1 ependymal cells. As neur...
Source: Cellular and Molecular Life Sciences : CMLS - March 20, 2019 Category: Cytology Authors: Winokurow N, Schumacher S Tags: Cell Mol Life Sci Source Type: research

E2F1 mediates the downregulation of POLD1 in replicative senescence.
In this study, four potential CpG islands in the POLD1 promoter were found, and the methylation levels of the POLD1 promoter were increased in aging 2BS cells, WI-38 cells and peripheral blood lymphocytes, especially at a single site, CpG 36, in CpG island 3. Then, the transcription factor E2F1 was observed to bind to these sites. The binding affinity of E2F1 for the POLD1 promoter was found to show age-related attenuation and was confirmed to be positively regulated by the E2F1 level and negatively regulated by POLD1 promoter methylation. Moreover, cell senescence characteristics were observed in the cells transfected wit...
Source: Cellular and Molecular Life Sciences : CMLS - March 20, 2019 Category: Cytology Authors: Gao S, Song Q, Liu J, Zhang X, Ji X, Wang P Tags: Cell Mol Life Sci Source Type: research

Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography.
ura S, Borràs FE Abstract Extracellular vesicles (EVs) include a variety of nanosized vesicles released to the extracellular microenvironment by the vast majority of cells transferring bioactive lipids, proteins, mRNA, miRNA or non-coding RNA, as means of intercellular communication. Remarkably, among other fields of research, their use has become promising for immunomodulation, tissue repair and as source for novel disease-specific molecular signatures or biomarkers. However, a major challenge is to define accurate, reliable and easily implemented techniques for EV isolation due to their nanoscale size and...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2019 Category: Cytology Authors: Monguió-Tortajada M, Gálvez-Montón C, Bayes-Genis A, Roura S, Borràs FE Tags: Cell Mol Life Sci Source Type: research

Mammalian haploid stem cells: establishment, engineering and applications.
Abstract Haploid embryonic stem cells (haESCs) contain only one set of genomes inherited from the sperm or egg and are termed AG- or PG-haESCs, respectively. Mammalian haESCs show genome-wide hypomethylation and dysregulated imprinting, whereas they can sustain genome integrity during derivation and long-term propagation. In addition, haESCs exhibit similar pluripotency to traditional diploid ESCs but are unique because they function as gametes and have been used to produce semi-cloned animals. More strikingly, unisexual reproduction has been achieved in mice by using haESCs. In combination with a gene editing or ...
Source: Cellular and Molecular Life Sciences : CMLS - March 19, 2019 Category: Cytology Authors: He W, Chen J, Gao S Tags: Cell Mol Life Sci Source Type: research

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia.
Abstract Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. These transdifferentiated VSMCs actively promote calcification in the medial layer of the arteries by producing...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Voelkl J, Lang F, Eckardt KU, Amann K, Kuro-O M, Pasch A, Pieske B, Alesutan I Tags: Cell Mol Life Sci Source Type: research

A critical role for miR-142 in alveolar epithelial lineage formation in mouse lung development.
We report that the activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased AT2 marker Sftpc and decreased miR-142 expression. Using miR-142 KO mice, we demonstrate an increase in the AT2/AT1 cell number ratio. Overexpression of miR-142 in alveolar progenitor cells in vivo led to the opposite effect. Examination of the KO lungs at E18.5 revealed enhanced expression of miR-142 targets Apc, Ep300 and Kras associated with increased β-catenin and p-Erk signaling. Silencing of miR-142 expression in lung explants grown in vitro triggers enhanced Sftpc express...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Shrestha A, Carraro G, Nottet N, Vazquez-Armendariz AI, Herold S, Cordero J, Singh I, Wilhelm J, Barreto G, Morty R, El Agha E, Mari B, Chen C, Zhang JS, Chao CM, Bellusci S Tags: Cell Mol Life Sci Source Type: research

LION: a simple and rapid method to achieve CRISPR gene editing.
Abstract The RNA-guided CRISPR-Cas9 technology has paved the way for rapid and cost-effective gene editing. However, there is still a great need for effective methods for rapid generation and validation of CRISPR/Cas9 gRNAs. Previously, we have demonstrated that highly efficient generation of multiplexed CRISPR guide RNA (gRNA) expression array can be achieved with Golden Gate Assembly (GGA). Here, we present an optimized and rapid method for generation and validation in less than 1 day of CRISPR gene targeting vectors. The method (LION) is based on ligation of double-stranded gRNA oligos into CRISPR vectors ...
Source: Cellular and Molecular Life Sciences : CMLS - March 18, 2019 Category: Cytology Authors: Xiang X, Luo L, Nodzyński M, Li C, Han P, Dou H, Petersen TS, Liang X, Pan X, Qu K, Yang L, Dang Y, Liu X, Bolund L, Zhang X, Tong G, Xing Y, Luo Y, Lin L Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.
Abstract The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been ...
Source: Cellular and Molecular Life Sciences : CMLS - March 16, 2019 Category: Cytology Authors: Mishra S, Verma SS, Rai V, Awasthee N, Chava S, Hui KM, Kumar AP, Challagundla KB, Sethi G, Gupta SC Tags: Cell Mol Life Sci Source Type: research

Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis.
Abstract Many secreted peptides used for cell-cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Recent studies have revealed that in addition to playing a key role in peptidergic signaling, PAM also regulates ciliogenesis in vertebrates, ...
Source: Cellular and Molecular Life Sciences : CMLS - March 16, 2019 Category: Cytology Authors: Kumar D, Mains RE, Eipper BA, King SM Tags: Cell Mol Life Sci Source Type: research

Proteins with calmodulin-like domains: structures and functional roles.
erchtold MW Abstract The appearance of modular proteins is a widespread phenomenon during the evolution of proteins. The combinatorial arrangement of different functional and/or structural domains within a single polypeptide chain yields a wide variety of activities and regulatory properties to the modular proteins. In this review, we will discuss proteins, that in addition to their catalytic, transport, structure, localization or adaptor functions, also have segments resembling the helix-loop-helix EF-hand motifs found in Ca2+-binding proteins, such as calmodulin (CaM). These segments are denoted CaM-like domains...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2019 Category: Cytology Authors: Villalobo A, González-Muñoz M, Berchtold MW Tags: Cell Mol Life Sci Source Type: research

Cancer targeting peptides.
Abstract Despite continuing advances in the development of biomacromolecules for therapeutic purposes, successful application of these often large and hydrophilic molecules has been hindered by their inability to efficiently traverse the cellular plasma membrane. In recent years, cell-penetrating peptides (CPPs) have received considerable attention as a promising class of delivery vectors due to their ability to mediate the efficient import of a large number of cargoes in vitro and in vivo. However, the lack of target specificity of CPPs remains a major obstacle to their clinical development. To address this issue...
Source: Cellular and Molecular Life Sciences : CMLS - March 15, 2019 Category: Cytology Authors: Kalmouni M, Al-Hosani S, Magzoub M Tags: Cell Mol Life Sci Source Type: research

To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.
Abstract Accumulating evidence has reached the consensus that the balance of phosphorylation state of signaling molecules is a pivotal point in the regulation of cell signaling. Therefore, characterizing elements (kinases-phosphatases) in the phosphorylation balance are at great importance. However, the role of phosphatase enzymes is less investigated than kinase enzymes. PP2A is a member of serine/threonine protein phosphatase that its imbalance has been reported in neurodegenerative diseases. Therefore, we reviewed the superfamily of phosphatases and more specifically PP2A, its regulation, and physiological func...
Source: Cellular and Molecular Life Sciences : CMLS - March 14, 2019 Category: Cytology Authors: Javadpour P, Dargahi L, Ahmadiani A, Ghasemi R Tags: Cell Mol Life Sci Source Type: research

Neutrophil pyroptosis: new perspectives on sepsis.
Abstract Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to fun...
Source: Cellular and Molecular Life Sciences : CMLS - March 14, 2019 Category: Cytology Authors: Liu L, Sun B Tags: Cell Mol Life Sci Source Type: research

Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models.
Abstract The Tar DNA-Binding Protein 43 (TDP-43) and its phosphorylated isoform (pTDP-43) are the major components associated with ubiquitin positive/Tau-negative inclusions found in neurons and glial cells of patients suffering of amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration-TDP-43 (FTLD-TDP). Many studies have revealed that TDP-43 is also in the protein inclusions associated with neurodegenerative conditions other than ALS and FTLD-TDP, thus suggesting that this protein may be involved in the pathogenesis of a variety of neurological disorders. In brains of Huntington-affected patient...
Source: Cellular and Molecular Life Sciences : CMLS - March 12, 2019 Category: Cytology Authors: Coudert L, Nonaka T, Bernard E, Hasegawa M, Schaeffer L, Leblanc P Tags: Cell Mol Life Sci Source Type: research

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.
Abstract Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Here, we have developed new methods for the non-subjective quantification of mitochondrial morphology in muscle and neuronal cells of Caenorhabditis elegans. Using these techniques, we uncover surprising tissue-specific differences in...
Source: Cellular and Molecular Life Sciences : CMLS - March 6, 2019 Category: Cytology Authors: Byrne JJ, Soh MS, Chandhok G, Vijayaraghavan T, Teoh JS, Crawford S, Cobham AE, Yapa NMB, Mirth CK, Neumann B Tags: Cell Mol Life Sci Source Type: research

From neural crest cells to melanocytes: cellular plasticity during development and beyond.
Abstract Here, we review melanocyte development and how the embryonic melanoblast, although specified to become a melanocyte, is prone to cellular plasticity and is not fully committed to the melanocyte lineage. Even fully differentiated and pigment-producing melanocytes do not always have a stable phenotype. The gradual lineage restriction of neural crest cells toward the melanocyte lineage is determined by both cell-intrinsic and extracellular signals in which differentiation and pathfinding ability reciprocally influence each other. These signals are leveraged by subtle differences in timing and axial positioni...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Vandamme N, Berx G Tags: Cell Mol Life Sci Source Type: research

Rab18: new insights into the function of an essential protein.
Abstract Rab18 is one of the small number of conserved Rab proteins which have been traced to the last eukaryotic common ancestor. It is found in organisms ranging from humans to trypanosomes, and localizes to multiple organelles, including most notably endoplasmic reticulum and lipid droplets. In humans, absence of Rab18 leads to a severe illness known as Warburg-Micro syndrome. Despite this evidence that Rab18 is essential, its role in cells remains mysterious. However, recent studies identifying effectors and interactors of Rab18, are now shedding light on its mechanism of action, suggesting functions related t...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Dejgaard SY, Presley JF Tags: Cell Mol Life Sci Source Type: research

Rab6 regulates cell migration and invasion by recruiting Cdc42 and modulating its activity.
Abstract Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood. In this work, we identify Rab6 as a negative regulator of cell m...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Vestre K, Kjos I, Guadagno NA, Borg Distefano M, Kohler F, Fenaroli F, Bakke O, Progida C Tags: Cell Mol Life Sci Source Type: research

Enhanced cerebral branched-chain amino acid metabolism in R6/2 mouse model of Huntington's disease.
petersen HS Abstract Huntington's disease (HD) is a hereditary and fatal disease causing profound neurodegeneration. Deficits in cerebral energy and neurotransmitter metabolism have been suggested to play a central role in the neuronal dysfunction and death associated with HD. The branched-chain amino acids (BCAAs), leucine, isoleucine and valine, are important for cerebral nitrogen homeostasis, neurotransmitter recycling and can be utilized as energy substrates in the tricarboxylic acid (TCA) cycle. Reduced levels of BCAAs in HD have been validated by several reports. However, it is still unknown how cerebral BCA...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Andersen JV, Skotte NH, Aldana BI, Nørremølle A, Waagepetersen HS Tags: Cell Mol Life Sci Source Type: research

Abnormalities in chemokine receptor recycling in chronic lymphocytic leukemia.
Abstract In addition to their modulation through de novo expression and degradation, surface levels of chemokine receptors are tuned by their ligand-dependent recycling to the plasma membrane, which ensures that engaged receptors become rapidly available for further rounds of signaling. Dysregulation of this process contributes to the pathogenesis of chronic lymphocytic leukemia (CLL) by enhancing surface expression of chemokine receptors, thereby favoring leukemic cell accumulation in the protective niche of lymphoid organs. In this review, we summarize our current understanding of the process of chemokine recept...
Source: Cellular and Molecular Life Sciences : CMLS - March 4, 2019 Category: Cytology Authors: Patrussi L, Capitani N, Baldari CT Tags: Cell Mol Life Sci Source Type: research

LRSAM1 E3 ubiquitin ligase: molecular neurobiological perspectives linked with brain diseases.
Abstract Cellular protein quality control (PQC) plays a significant role in the maintenance of cellular homeostasis. Failure of PQC mechanism may lead to various neurodegenerative diseases due to accumulation of aberrant proteins. To avoid such fatal neuronal conditions PQC employs autophagy and ubiquitin proteasome system (UPS) to degrade misfolded proteins. Few quality control (QC) E3 ubiquitin ligases interplay an important role to specifically recognize misfolded proteins for their intracellular degradation. Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) is a really interesting new gene (RIN...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2019 Category: Cytology Authors: Mishra R, Upadhyay A, Prajapati VK, Dhiman R, Poluri KM, Jana NR, Mishra A Tags: Cell Mol Life Sci Source Type: research

Anti-inflammatory cytokines in endometriosis.
Abstract Although the pathogenesis of endometriosis is not fully understood, it is often considered to be an inflammatory disease. An increasing number of studies suggest that differential expression of anti-inflammatory cytokines (e.g., interleukin-4 and -10, and transforming growth factor-β1) occurs in women with endometriosis, including in serum, peritoneal fluid and ectopic lesions. These anti-inflammatory cytokines also have indispensable roles in the progression of endometriosis, including by promoting survival, growth, invasion, differentiation, angiogenesis, and immune escape of the endometriotic...
Source: Cellular and Molecular Life Sciences : CMLS - March 2, 2019 Category: Cytology Authors: Zhou WJ, Yang HL, Shao J, Mei J, Chang KK, Zhu R, Li MQ Tags: Cell Mol Life Sci Source Type: research

Establishment and depletion of the ovarian reserve: physiology and impact of environmental chemicals.
In conclusion, evidences exist that exposure to RTECs can compromise a woman's reproductive health. However, human exposures may date back to the developmental stage, while the adverse effects are usually diagnosed decades later, thus making it difficult to determine the association between RTECs exposure and human reproductive health. Therefore, epidemiological surveys and more experimental investigation on humans, or alternatively primates, are needed to determine the direct and indirect effects caused by RTECs exposure on the ovary function, and to characterize their action mechanisms. PMID: 30810760 [PubMed - as s...
Source: Cellular and Molecular Life Sciences : CMLS - February 27, 2019 Category: Cytology Authors: Ge W, Li L, Dyce PW, De Felici M, Shen W Tags: Cell Mol Life Sci Source Type: research

Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance.
Abstract Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the abil...
Source: Cellular and Molecular Life Sciences : CMLS - February 25, 2019 Category: Cytology Authors: Braicu C, Zimta AA, Gulei D, Olariu A, Berindan-Neagoe I Tags: Cell Mol Life Sci Source Type: research

Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate.
In this study, we unlock this critical bottleneck, by reporting an efficient expression and purification system of recombinant HSulf-2 in mammalian HEK293 cells. This novel source of enzyme enabled us to investigate the way the enzyme domain organization dictates its functional properties. By generating mutants, we confirmed previous studies that HSulf-2 catalytic (CAT) domain was sufficient to elicit arylsulfatase activity and that its hydrophilic (HD) domain was necessary for the enzyme 6-O-endosulfatase activity. However, we demonstrated for the first time that high-affinity binding of HS substrates occurred through the...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Seffouh A, El Masri R, Makshakova O, Gout E, Hassoun ZEO, Andrieu JP, Lortat-Jacob H, Vivès RR Tags: Cell Mol Life Sci Source Type: research

Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain.
Abstract Chronic neuropathic pain is a debilitating condition that remains challenging to treat. Glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been used to treat neuropathic pain, but the exact sites of their actions have been unclear until recently. Although conventionally postsynaptic, NMDARs are also expressed presynaptically, particularly at the central terminals of primary sensory neurons, in the spinal dorsal horn. However, presynaptic NMDARs in the spinal cord are normally quiescent and are not actively involved in physiological nociceptive transmission. In this review, we describe the em...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Deng M, Chen SR, Pan HL Tags: Cell Mol Life Sci Source Type: research

RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding.
Abstract RDH1 is one of the several enzymes that catalyze the first of the two reactions to convert retinol into all-trans-retinoic acid (atRA). Here, we show that Rdh1-null mice fed a low-fat diet gain more weight as adiposity (17% males, 13% females) than wild-type mice by 20 weeks old, despite neither consuming more calories nor decreasing activity. Glucose intolerance and insulin resistance develop following increased adiposity. Despite the increase in white fat pads, epididymal white adipose does not express Rdh1, nor does muscle. Brown adipose tissue (BAT) and liver express Rdh1 at relatively high level...
Source: Cellular and Molecular Life Sciences : CMLS - February 20, 2019 Category: Cytology Authors: Krois CR, Vuckovic MG, Huang P, Zaversnik C, Liu CS, Gibson CE, Wheeler MR, Obrochta KM, Min JH, Herber CB, Thompson AC, Shah ID, Gordon SP, Hellerstein MK, Napoli JL Tags: Cell Mol Life Sci Source Type: research