Cancellation of nerve excitation by the reversal of nanosecond stimulus polarity and its relevance to the gating time of sodium channels.
Abstract The initiation of action potentials (APs) by membrane depolarization occurs after a brief vulnerability period, during which excitation can be abolished by the reversal of the stimulus polarity. This vulnerability period is determined by the time needed for gating of voltage-gated sodium channels (VGSC). We compared nerve excitation by ultra-short uni- and bipolar stimuli to define the time frame of bipolar cancellation and of AP initiation. Propagating APs in isolated frog sciatic nerve were elicited by cathodic pulses (200 ns-300 µs), followed by an anodic (canceling) pulse of the same d...
Source: Cellular and Molecular Life Sciences : CMLS - May 3, 2019 Category: Cytology Authors: Casciola M, Xiao S, Apollonio F, Paffi A, Liberti M, Muratori C, Pakhomov AG Tags: Cell Mol Life Sci Source Type: research

Novel insights into PARPs in gene expression: regulation of RNA metabolism.
Abstract Poly(ADP-ribosyl)ation (PARylation) is an important post-translational modification in which an ADP-ribose group is transferred to the target protein by poly(ADP-riboses) polymerases (PARPs). Since the discovery of poly-ADP-ribose (PAR) 50 years ago, its roles in cellular processes have been extensively explored. Although research initially focused on the functions of PAR and PARPs in DNA damage detection and repair, our understanding of the roles of PARPs in various nuclear and cytoplasmic processes, particularly in gene expression, has increased significantly. In this review, we discuss the current...
Source: Cellular and Molecular Life Sciences : CMLS - May 3, 2019 Category: Cytology Authors: Ke Y, Zhang J, Lv X, Zeng X, Ba X Tags: Cell Mol Life Sci Source Type: research

The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification.
Szakács G Abstract ABCB6 belongs to the family of ATP-binding cassette (ABC) transporters, which transport various molecules across extra- and intra-cellular membranes, bearing significant impact on human disease and pharmacology. Although mutations in the ABCB6 gene have been linked to a variety of pathophysiological conditions ranging from transfusion incompatibility to pigmentation defects, its precise cellular localization and function is not understood. In particular, the intracellular localization of ABCB6 has been a matter of debate, with conflicting reports suggesting mitochondrial or endolysosomal...
Source: Cellular and Molecular Life Sciences : CMLS - May 2, 2019 Category: Cytology Authors: Rakvács Z, Kucsma N, Gera M, Igriczi B, Kiss K, Barna J, Kovács D, Vellai T, Bencs L, Reisecker JM, Szoboszlai N, Szakács G Tags: Cell Mol Life Sci Source Type: research

The effect and molecular mechanism of statins on the expression of human anti-coagulation genes.
Abstract Statins are potent lipid-lowering drugs. Large prospective clinical trials have shown the anti-thrombotic effect of statins, e.g., preventing deep vein thrombosis. However, the mechanism underlying the beneficial effect of statins in reducing thrombus formation remains to be established. We, thus, conduct this study to investigate the potential molecular mechanisms. The cultured human hepatoma cells (HepG2) were used as the in vitro model. The human protein C gene promoter was cloned into the luciferase reporter to study the transcriptional regulation of human protein C gene. Wistar rats fed with simvasta...
Source: Cellular and Molecular Life Sciences : CMLS - May 2, 2019 Category: Cytology Authors: Chang SN, Wu CK, Lai LP, Chiang FT, Hwang JJ, Tsai CT Tags: Cell Mol Life Sci Source Type: research

KIF2A characterization after spinal cord injury.
Abstract Axons in the central nervous system (CNS) typically fail to regenerate after injury. This failure is multi-factorial and caused in part by disruption of the axonal cytoskeleton. The cytoskeleton, in particular microtubules (MT), plays a critical role in axonal transport and axon growth during development. In this regard, members of the kinesin superfamily of proteins (KIFs) regulate the extension of primary axons toward their targets and control the growth of collateral branches. KIF2A negatively regulates axon growth through MT depolymerization. Using three different injury models to induce SCI in adult ...
Source: Cellular and Molecular Life Sciences : CMLS - April 29, 2019 Category: Cytology Authors: Seira O, Liu J, Assinck P, Ramer M, Tetzlaff W Tags: Cell Mol Life Sci Source Type: research

Correction to: Dgcr8 knockout approaches to understand microRNA functions in vitro and in vivo.
Abstract The section: "miRNA‑independent functions of DICER" was missed between the section "miRNA‑independent functions of DROSHA and DGCR8" and the section "The Dgcr8 knockout strategy to study miRNA functions" in the original publications. PMID: 31037335 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2019 Category: Cytology Authors: Guo WT, Wang Y Tags: Cell Mol Life Sci Source Type: research

Intrinsic and extrinsic mechanisms of synapse formation and specificity in C. elegans.
Abstract Precise neuronal wiring is critical for the function of the nervous system and is ultimately determined at the level of individual synapses. Neurons integrate various intrinsic and extrinsic cues to form synapses onto their correct targets in a stereotyped manner. In the past decades, the nervous system of nematode (Caenorhabditis elegans) has provided the genetic platform to reveal the genetic and molecular mechanisms of synapse formation and specificity. In this review, we will summarize the recent discoveries in synapse formation and specificity in C. elegans. PMID: 31037336 [PubMed - as supplied ...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2019 Category: Cytology Authors: Hendi A, Kurashina M, Mizumoto K Tags: Cell Mol Life Sci Source Type: research

Multiple roles of CTDK-I throughout the cell.
Abstract The heterotrimeric carboxy-terminal domain kinase I (CTDK-I) in yeast is a cyclin-dependent kinase complex that is evolutionally conserved throughout eukaryotes and phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (RNApII) on the second-position serine (Ser2) residue of YSPTSPS heptapeptide repeats. CTDK-I plays indispensable roles in transcription elongation and transcription-coupled processing, such as the 3'-end processing of nascent mRNA transcripts. However, recent studies have revealed additional roles of CTDK-I beyond its primary effect on transcription by RNApII. He...
Source: Cellular and Molecular Life Sciences : CMLS - April 28, 2019 Category: Cytology Authors: Srivastava R, Duan R, Ahn SH Tags: Cell Mol Life Sci Source Type: research

Advances in targeted degradation of endogenous proteins.
GP Abstract Protein silencing is often employed as a means to aid investigations in protein function and is increasingly desired as a therapeutic approach. Several types of protein silencing methodologies have been developed, including targeting the encoding genes, transcripts, the process of translation or the protein directly. Despite these advances, most silencing systems suffer from limitations. Silencing protein expression through genetic ablation, for example by CRISPR/Cas9 genome editing, is irreversible, time consuming and not always feasible. Similarly, RNA interference approaches warrant prolonged treat...
Source: Cellular and Molecular Life Sciences : CMLS - April 26, 2019 Category: Cytology Authors: Röth S, Fulcher LJ, Sapkota GP Tags: Cell Mol Life Sci Source Type: research

Expanded targeting scope and enhanced base editing efficiency in rabbit using optimized xCas9(3.7).
Abstract Evolved xCas9(3.7) variant with broad PAM compatibility has been reported in cell lines, while its editing efficiency was site-specific. Here, we show that xCas9(3.7) can recognize a broad PAMs including NGG, NGA, and NGT, in both embryos and Founder (F0) rabbits. Furthermore, the codon-optimized xCas9-derived base editors, exBE4 and exABE, can dramatically improve the base editing efficiencies in rabbit embryos. Our results demonstrated that the optimized xCas9 with expanded PAM compatibility and enhanced base editing efficiency could be used for precise gene modifications in organisms. PMID: 310302...
Source: Cellular and Molecular Life Sciences : CMLS - April 26, 2019 Category: Cytology Authors: Liu Z, Chen M, Shan H, Chen S, Xu Y, Song Y, Zhang Q, Yuan H, Ouyang H, Li Z, Lai L Tags: Cell Mol Life Sci Source Type: research

Crosstalk between chitosan and cell signaling pathways.
Abstract The field of tissue engineering (TE) experiences its most exciting time in the current decade. Recent progresses in TE have made it able to translate into clinical applications. To regenerate damaged tissues, TE uses biomaterial scaffolds to prepare a suitable backbone for tissue regeneration. It is well proven that the cell-biomaterial crosstalk impacts tremendously on cell biological activities such as differentiation, proliferation, migration, and others. Clarification of exact biological effects and mechanisms of a certain material on various cell types promises to have a profound impact on clinical a...
Source: Cellular and Molecular Life Sciences : CMLS - April 26, 2019 Category: Cytology Authors: Farhadihosseinabadi B, Zarebkohan A, Eftekhary M, Heiat M, Moosazadeh Moghaddam M, Gholipourmalekabadi M Tags: Cell Mol Life Sci Source Type: research

Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors.
T, Dede K, Bursics A, Buzás EI, Zeöld A, Wiener Z Abstract Extracellular vesicles (EVs) are membrane-surrounded structures that transmit biologically important molecules from the releasing to target cells, thus providing a novel intercellular communication mechanism. Since EVs carry their cargo in a protected form and their secretion is generally increased in tumorigenesis, EVs hold a great potential for early cancer diagnosis. By 3D culturing, we provide evidence that colorectal cancer (CRC) patient-derived organoids, representing a state-of-the-art established and essential approach for studying huma...
Source: Cellular and Molecular Life Sciences : CMLS - April 25, 2019 Category: Cytology Authors: Szvicsek Z, Oszvald Á, Szabó L, Sándor GO, Kelemen A, Soós AÁ, Pálóczi K, Harsányi L, Tölgyes T, Dede K, Bursics A, Buzás EI, Zeöld A, Wiener Z Tags: Cell Mol Life Sci Source Type: research

The evolutionary landscape of the Rab family in chordates.
Abstract Intracellular traffic amongst organelles represents a key feature for eukaryotes and is orchestrated principally by members of Rab family, the largest within Ras superfamily. Given that variations in Rab repertoire have been fundamental in animal diversification, we provided the most exhaustive survey regarding the Rab toolkit of chordates. Our findings reveal the existence of 42 metazoan conserved subfamilies exhibiting a univocal intron/exon structure preserved from cnidarians to vertebrates. Since the current view does not capture the Rab complexity, we propose a new Rab family classification in t...
Source: Cellular and Molecular Life Sciences : CMLS - April 25, 2019 Category: Cytology Authors: Coppola U, Ristoratore F, Albalat R, D'Aniello S Tags: Cell Mol Life Sci Source Type: research

Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms.
oistinaho J Abstract Astrocytes are the most abundant cell type in the brain. They were long considered only as passive support for neuronal cells. However, recent data have revealed many active roles for these cells both in maintenance of the normal physiological homeostasis in the brain as well as in neurodegeneration and disease. Moreover, human astrocytes have been found to be much more complex than their rodent counterparts, and to date, astrocytes are known to actively participate in a multitude of processes such as neurotransmitter uptake and recycling, gliotransmitter release, neuroenergetics, inflammation...
Source: Cellular and Molecular Life Sciences : CMLS - April 22, 2019 Category: Cytology Authors: Oksanen M, Lehtonen S, Jaronen M, Goldsteins G, Hämäläinen RH, Koistinaho J Tags: Cell Mol Life Sci Source Type: research

Network mapping of the conformational heterogeneity of SOD1 by deploying statistical cluster analysis of FTIR spectra.
This study provides a quantifiable picture of how conformational information at one particular site (for example, the copper-binding pocket) is related to the information at the second site (for example, the zinc-binding pocket), and how this relatedness is transferred to the global conformational information of the protein. The distance outputs were used to quantitatively generate a network capturing the folding sub-stages of SOD1. PMID: 31011770 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 21, 2019 Category: Cytology Authors: Chowdhury S, Sen S, Banerjee A, Uversky VN, Maulik U, Chattopadhyay K Tags: Cell Mol Life Sci Source Type: research

Helicobacter pylori infection and gastrointestinal tract cancer biology: considering a double-edged sword reflection.
PMID: 31006036 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2019 Category: Cytology Authors: Kountouras J, Doulberis M, Papaefthymiou A, Polyzos SA, Touloumtzi M, Elisabeth V, Kapetanakis N, Liatsos C, Gavalas E, Katsinelos P Tags: Cell Mol Life Sci Source Type: research

NEAT1 regulates neuroglial cell mediating A β clearance via the epigenetic regulation of endocytosis-related genes expression.
NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis-related genes expression. Cell Mol Life Sci. 2019 Apr 20;: Authors: Wang Z, Zhao Y, Xu N, Zhang S, Wang S, Mao Y, Zhu Y, Li B, Jiang Y, Tan Y, Xie W, Yang BB, Zhang Y Abstract The accumulation of intracellular β-amyloid peptide (Aβ) is important pathological characteristic of Alzheimer's disease (AD). However, the exact underlying molecular mechanism remains to be elucidated. Here, we reported that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), a long n on-coding RNA, exhibits repress...
Source: Cellular and Molecular Life Sciences : CMLS - April 19, 2019 Category: Cytology Authors: Wang Z, Zhao Y, Xu N, Zhang S, Wang S, Mao Y, Zhu Y, Li B, Jiang Y, Tan Y, Xie W, Yang BB, Zhang Y Tags: Cell Mol Life Sci Source Type: research

Characterization of PPIB interaction in the P3H1 ternary complex and implications for its pathological mutations.
Abstract The P3H1/CRTAP/PPIB complex is essential for prolyl 3-hydroxylation and folding of procollagens in the endoplasmic reticulum (ER). Deficiency in any component of this ternary complex is associated with the misfolding of collagen and the onset of osteogenesis imperfecta. However, little structure information is available about how this ternary complex is assembled and retained in the ER. Here, we assessed the role of the KDEL sequence of P3H1 and probed the spatial interactions of PPIB in the complex. We show that the KDEL sequence is essential for retaining the P3H1 complex in the ER. Its removal resulted...
Source: Cellular and Molecular Life Sciences : CMLS - April 15, 2019 Category: Cytology Authors: Wu J, Zhang W, Xia L, Feng L, Shu Z, Zhang J, Ye W, Zeng N, Zhou A Tags: Cell Mol Life Sci Source Type: research

Bcl-2 and IP3 compete for the ligand-binding domain of IP3Rs modulating Ca2+ signaling output.
Abstract Bcl-2 proteins have emerged as critical regulators of intracellular Ca2+ dynamics by directly targeting and inhibiting the IP3 receptor (IP3R), a major intracellular Ca2+-release channel. Here, we demonstrate that such inhibition occurs under conditions of basal, but not high IP3R activity, since overexpressed and purified Bcl-2 (or its BH4 domain) can inhibit IP3R function provoked by low concentration of agonist or IP3, while fails to attenuate against high concentration of agonist or IP3. Surprisingly, Bcl-2 remained capable of inhibiting IP3R1 channels lacking the residues encompassing the previo...
Source: Cellular and Molecular Life Sciences : CMLS - April 15, 2019 Category: Cytology Authors: Ivanova H, Wagner LE, Tanimura A, Vandermarliere E, Luyten T, Welkenhuyzen K, Alzayady KJ, Wang L, Hamada K, Mikoshiba K, De Smedt H, Martens L, Yule DI, Parys JB, Bultynck G Tags: Cell Mol Life Sci Source Type: research

Dysregulation of histone deacetylases in carcinogenesis and tumor progression: a possible link to apoptosis and autophagy.
Abstract Dysregulation of the epigenome and constitutional epimutation lead to aberrant expression of the genes, which regulate cancer initiation and progression. Histone deacetylases (HDACs), which are highly conserved in yeast to humans, are known to regulate numerous proteins involved in the transcriptional regulation of chromatin structures, apoptosis, autophagy, and mitophagy. In addition, a non-permissive chromatin conformation is created by HDACs, preventing the transcription of the genes encoding the proteins associated with tumorigenesis. Recently, an expanding perspective has been reported from the clini...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Patra S, Panigrahi DP, Praharaj PP, Bhol CS, Mahapatra KK, Mishra SR, Behera BP, Jena M, Bhutia SK Tags: Cell Mol Life Sci Source Type: research

Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is the fourth leading cause of cancer-related death and is associated with a very poor prognosis. KRAS driver mutations occur in approximately 95% of PDAC cases and cause the activation of several signaling pathways such as mitogen-activated protein kinase (MAPK) pathways. Regulation of these signaling pathways is orchestrated by feedback loops mediated by the balance between protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), leading to activation or inhibition of its downstream targets. The hum...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Ruckert MT, de Andrade PV, Santos VS, Silveira VS Tags: Cell Mol Life Sci Source Type: research

Computational algorithms for in silico profiling of activating mutations in cancer.
Abstract Methods to catalog and computationally assess the mutational landscape of proteins in human cancers are desirable. One approach is to adapt evolutionary or data-driven methods developed for predicting whether a single-nucleotide polymorphism (SNP) is deleterious to protein structure and function. In cases where understanding the mechanism of protein activation and regulation is desired, an alternative approach is to employ structure-based computational approaches to predict the effects of point mutations. Through a case study of mutations in kinase domains of three proteins, namely, the anaplastic lymphom...
Source: Cellular and Molecular Life Sciences : CMLS - April 12, 2019 Category: Cytology Authors: Jordan EJ, Patil K, Suresh K, Park JH, Mosse YP, Lemmon MA, Radhakrishnan R Tags: Cell Mol Life Sci Source Type: research

The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis.
Abstract Spermatogenesis is fundamental to the establishment and maintenance of male reproduction, whereas its abnormality results in male infertility. Somatic cells, including Leydig cells, myoid cells, and Sertoli cells, constitute the microenvironment or the niche of testis, which is essential for regulating normal spermatogenesis. Leydig cells are an important component of the testicular stroma, while peritubular myoid cells are one of the major cell types of seminiferous tubules. Here we addressed the roles and mechanisms of Leydig cells and myoid cells in the regulation of spermatogenesis. Specifically, we s...
Source: Cellular and Molecular Life Sciences : CMLS - April 11, 2019 Category: Cytology Authors: Zhou R, Wu J, Liu B, Jiang Y, Chen W, Li J, He Q, He Z Tags: Cell Mol Life Sci Source Type: research

Fbxo30 regulates chromosome segregation of oocyte meiosis.
In this report, we find that Fbxo30, a new member of F-box proteins, is enriched in mouse oocytes, and its expression level declines substantially after the metaphase of the first meiosis (MI). Notably, depletion of Fbxo30 causes significant chromosome compaction accompanied by chromosome segregation failure and arrest at the MI stage, and this arrest is not caused by over-activation of spindle assembly checkpoint. Using immunoprecipitation and mass spectrometric analysis, we identify stem-loop-binding protein (SLBP) as a novel substrate of Fbxo30. SLBP overexpression caused by Fbxo30 depletion results in a remarkable over...
Source: Cellular and Molecular Life Sciences : CMLS - April 11, 2019 Category: Cytology Authors: Jin Y, Yang M, Gao C, Yue W, Liang X, Xie B, Zhu X, Fan S, Li R, Li M Tags: Cell Mol Life Sci Source Type: research

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 11, 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 11, 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 11, 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 11, 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 10, 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 10, 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 8, 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 4, 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 4, 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 3, 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 2, 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 2, 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 - March 31, 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 29, 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 28, 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 27, 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 26, 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 26, 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 26, 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 24, 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 22, 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 22, 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 21, 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 19, 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 19, 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 18, 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