Epsins in vascular development, function and disease.
Abstract Epsins are a family of adaptor proteins involved in clathrin-dependent endocytosis. In the vasculature, epsins 1 and 2 are functionally redundant members of this family that are expressed in the endothelial cells of blood vessels and the lymphatic system throughout development and adulthood. These proteins contain a number of peptide motifs that allow them to interact with lipid moieties and a variety of proteins. These interactions facilitate the regulation of a wide range of cell signaling pathways. In this review, we focus on the involvement of epsins 1 and 2 in controlling vascular endothelial growth ...
Source: Cellular and Molecular Life Sciences : CMLS - September 14, 2020 Category: Cytology Authors: Bhattacharjee S, Lee Y, Zhu B, Wu H, Chen Y, Chen H Tags: Cell Mol Life Sci Source Type: research

Differential effects of putative N-glycosylation sites in human Tau on Alzheimer's disease-related neurodegeneration.
Abstract Amyloid assemblies of Tau are associated with Alzheimer's disease (AD). In AD Tau undergoes several abnormal post-translational modifications, including hyperphosphorylation and glycosylation, which impact disease progression. N-glycosylated Tau was reported to be found in AD brain tissues but not in healthy counterparts. This is surprising since Tau is a cytosolic protein whereas N-glycosylation occurs in the ER-Golgi. Previous in vitro studies indicated that N-glycosylation of Tau facilitated its phosphorylation and contributed to maintenance of its Paired Helical Filament structure. However, the specif...
Source: Cellular and Molecular Life Sciences : CMLS - September 13, 2020 Category: Cytology Authors: Losev Y, Frenkel-Pinter M, Abu-Hussien M, Viswanathan GK, Elyashiv-Revivo D, Geries R, Khalaila I, Gazit E, Segal D Tags: Cell Mol Life Sci Source Type: research

Intercellular trafficking via plasmodesmata: molecular layers of complexity.
Abstract Plasmodesmata are intercellular pores connecting together most plant cells. These structures consist of a central constricted form of the endoplasmic reticulum, encircled by some cytoplasmic space, in turn delimited by the plasma membrane, itself ultimately surrounded by the cell wall. The presence and structure of plasmodesmata create multiple routes for intercellular trafficking of a large spectrum of molecules (encompassing RNAs, proteins, hormones and metabolites) and also enable local signalling events. Movement across plasmodesmata is finely controlled in order to balance processes requiring co...
Source: Cellular and Molecular Life Sciences : CMLS - September 11, 2020 Category: Cytology Authors: Li ZP, Paterlini A, Glavier M, Bayer EM Tags: Cell Mol Life Sci Source Type: research

Interplay between HMGA and TP53 in cell cycle control along tumor progression.
Abstract The high mobility group A (HMGA) proteins are found to be aberrantly expressed in several tumors. Studies (in vitro and in vivo) have shown that HMGA protein overexpression has a causative role in carcinogenesis process. HMGA proteins regulate cell cycle progression through distinct mechanisms which strongly influence its normal dynamics along malignant transformation. Tumor protein p53 (TP53) is the most frequently altered gene in cancer. The loss of its activity is recognized as the fall of a barrier that enables neoplastic transformation. Among the different functions, TP53 signaling pathway is tightly...
Source: Cellular and Molecular Life Sciences : CMLS - September 11, 2020 Category: Cytology Authors: Meireles Da Costa N, Palumbo A, De Martino M, Fusco A, Ribeiro Pinto LF, Nasciutti LE Tags: Cell Mol Life Sci Source Type: research

Motile cilia genetics and cell biology: big results from little mice.
Abstract Our understanding of motile cilia and their role in disease has increased tremendously over the last two decades, with critical information and insight coming from the analysis of mouse models. Motile cilia form on specific epithelial cell types and typically beat in a coordinated, whip-like manner to facilitate the flow and clearance of fluids along the cell surface. Defects in formation and function of motile cilia result in primary ciliary dyskinesia (PCD), a genetically heterogeneous disorder with a well-characterized phenotype but no effective treatment. A number of model systems, ranging from unicel...
Source: Cellular and Molecular Life Sciences : CMLS - September 10, 2020 Category: Cytology Authors: Lee L, Ostrowski LE Tags: Cell Mol Life Sci Source Type: research

NEAT1 polyA-modulating antisense oligonucleotides reveal opposing functions for both long non-coding RNA isoforms in neuroblastoma.
Abstract Many long non-coding RNAs (lncRNA) are highly dysregulated in cancer and are emerging as therapeutic targets. One example is NEAT1, which consists of two overlapping lncRNA isoforms, NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb), that are functionally distinct. The longer NEAT1_2 is responsible for scaffolding gene-regulatory nuclear bodies termed paraspeckles, whereas NEAT1_1 is involved in paraspeckle-independent function. The NEAT1 isoform ratio is dependent on the efficient cleavage and polyadenylation of NEAT1_1 at the expense of NEAT1_2. Here, we developed a targeted antisense oligonucleotide (ASO)...
Source: Cellular and Molecular Life Sciences : CMLS - September 9, 2020 Category: Cytology Authors: Naveed A, Cooper JA, Li R, Hubbard A, Chen J, Liu T, Wilton SD, Fletcher S, Fox AH Tags: Cell Mol Life Sci Source Type: research

FGF primes angioblast formation by inducing ETV2 and LMO2 via FGFR1/BRAF/MEK/ERK.
Abstract It is critical to specify a signal that directly drives the transition that occurs between cell states. However, such inferences are often confounded by indirect intercellular communications or secondary transcriptomic changes due to primary transcription factors. Although FGF is known for its importance during mesoderm-to-endothelium differentiation, its specific role and signaling mechanisms are still unclear due to the confounding factors referenced above. Here, we attempted to minimize the secondary artifacts by manipulating FGF and its downstream mediators with a short incubation time ...
Source: Cellular and Molecular Life Sciences : CMLS - September 9, 2020 Category: Cytology Authors: Chen PC, Hsueh YW, Lee YH, Tsai HW, Tsai KJ, Chiang PM Tags: Cell Mol Life Sci Source Type: research

Hedgehog signaling regulates regenerative patterning and growth in Harmonia axyridis leg.
Abstract Appendage regeneration has been widely studied in many species. Compared to other animal models, Harmonia axyridis has the advantage of a short life cycle, is easily reared, has strong regeneration capacity and contains systemic RNAi, making it a model organism for research on appendage regeneration. Here, we performed transcriptome analysis, followed by gene functional assays to reveal the molecular mechanism of H. axyridis leg regenerative growth process. Signaling pathways including Decapentaplegic (Dpp), Wingless (Wg), Ds/Ft/Hippo, Notch, Egfr, and Hedgehog (Hh) were all upregulated during the leg reg...
Source: Cellular and Molecular Life Sciences : CMLS - September 8, 2020 Category: Cytology Authors: Zhou H, Ma Z, Wang Z, Yan S, Wang D, Shen J Tags: Cell Mol Life Sci Source Type: research

Elevated post-ischemic ubiquitination results from suppression of deubiquitinase activity and not proteasome inhibition.
Abstract Cerebral ischemia-reperfusion increases intraneuronal levels of ubiquitinated proteins, but the factors driving ubiquitination and whether it results from altered proteostasis remain unclear. To address these questions, we used in vivo and in vitro models of cerebral ischemia-reperfusion, in which hippocampal slices were transiently deprived of oxygen and glucose to simulate ischemia followed by reperfusion, or the middle cerebral artery was temporarily occluded in mice. We found that post-ischemic ubiquitination results from two key steps: restoration of ATP at reperfusion, which allows initiation of pro...
Source: Cellular and Molecular Life Sciences : CMLS - September 4, 2020 Category: Cytology Authors: Kahles T, Poon C, Qian L, Palfini V, Srinivasan SP, Swaminathan S, Blanco I, Rodney-Sandy R, Iadecola C, Zhou P, Hochrainer K Tags: Cell Mol Life Sci Source Type: research

P53 in acute respiratory distress syndrome.
Abstract P53 is a tumor suppressor protein, associated with strong anti-inflammatory activities. Recent evidence suggest that this transcription factor counteracts lung inflammatory diseases, including the lethal acute respiratory distress syndrome. Herein we provide a brief discussion on the relevant topic. PMID: 32886127 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - September 3, 2020 Category: Cytology Authors: Barabutis N Tags: Cell Mol Life Sci Source Type: research

Cellular prion protein dysfunction in a prototypical inherited metabolic myopathy.
Abstract Inherited fatty acid oxidation diseases in their mild forms often present as metabolic myopathies. Carnitine Palmitoyl Transferase 2 (CPT2) deficiency, one such prototypical disorder is associated with compromised myotube differentiation. Here, we show that CPT2-deficient myotubes exhibit defects in focal adhesions and redox balance, exemplified by increased SOD2 expression. We document unprecedented alterations in the cellular prion protein PrPC, which directly arise from the failure in CPT2 enzymatic activity. We also demonstrate that the loss of PrPC function in normal myotubes recapitulates the defect...
Source: Cellular and Molecular Life Sciences : CMLS - August 31, 2020 Category: Cytology Authors: Boufroura FZ, Tomkiewicz-Raulet C, Poindessous V, Castille J, Vilotte JL, Bastin J, Mouillet-Richard S, Djouadi F Tags: Cell Mol Life Sci Source Type: research

DYRK1A: a down syndrome-related dual protein kinase with a versatile role in tumorigenesis.
Abstract Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a dual kinase that can phosphorylate its own activation loop on tyrosine residue and phosphorylate its substrates on threonine and serine residues. It is the most studied member of DYRK kinases, because its gene maps to human chromosome 21 within the Down syndrome critical region (DSCR). DYRK1A overexpression was found to be responsible for the phenotypic features observed in Down syndrome such as mental retardation, early onset neurodegenerative, and developmental heart defects. Besides its dual activity in phosphorylation, DYRK1A ...
Source: Cellular and Molecular Life Sciences : CMLS - August 31, 2020 Category: Cytology Authors: Laham AJ, Saber-Ayad M, El-Awady R Tags: Cell Mol Life Sci Source Type: research

Novel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas.
Abstract Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematological diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing glo...
Source: Cellular and Molecular Life Sciences : CMLS - August 25, 2020 Category: Cytology Authors: Jeitany M, Prabhu A, Dakle P, Pathak E, Madan V, Kanojia D, Mukundan V, Jiang YY, Landesman Y, Tam WL, Kappei D, Koeffler HP Tags: Cell Mol Life Sci Source Type: research

The pro-apoptotic domain of BIM protein forms toxic amyloid fibrils.
Abstract BIM is a key apoptotic protein, participating in diverse cellular processes. Interestingly, recent studies have hypothesized that BIM is associated with the extensive neuronal cell death encountered in protein misfolding diseases, such as Alzheimer's disease. Here, we report that the core pro-apoptotic domain of BIM, the BIM-BH3 motif, forms ubiquitous amyloid fibrils. The BIM-BH3 fibrils exhibit cytotoxicity, disrupt mitochondrial functions, and modulate the structures and dynamics of mitochondrial membrane mimics. Interestingly, a slightly longer peptide in which BIM-BH3 was flanked by four additional r...
Source: Cellular and Molecular Life Sciences : CMLS - August 24, 2020 Category: Cytology Authors: Malishev R, Ben-Zichri S, Oren O, Shauloff N, Peretz T, Taube R, Papo N, Jelinek R Tags: Cell Mol Life Sci Source Type: research

The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.
Abstract Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bio...
Source: Cellular and Molecular Life Sciences : CMLS - August 17, 2020 Category: Cytology Authors: Lei Y, Tang D, Liao G, Xu L, Liu S, Chen Q, Li C, Duan J, Wang K, Wang J, Sun B, Li Z, Dai L, Cheng W, Qi S, Lu K Tags: Cell Mol Life Sci Source Type: research

Sterile inflammation in thoracic transplantation.
Abstract The life-saving benefits of organ transplantation can be thwarted by allograft dysfunction due to both infectious and sterile inflammation post-surgery. Sterile inflammation can occur after necrotic cell death due to the release of endogenous ligands [such as damage-associated molecular patterns (DAMPs) and alarmins], which perpetuate inflammation and ongoing cellular injury via various signaling cascades. Ischemia-reperfusion injury (IRI) is a significant contributor to sterile inflammation after organ transplantation and is associated with detrimental short- and long-term outcomes. While the vicious cyc...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2020 Category: Cytology Authors: Frye CC, Bery AI, Kreisel D, Kulkarni HS Tags: Cell Mol Life Sci Source Type: research

Epidermal resident γδ T cell development and function in skin.
Epidermal resident γδ T cell development and function in skin. Cell Mol Life Sci. 2020 Aug 17;: Authors: Xu Y, Dimitrion P, Cvetkovski S, Zhou L, Mi QS Abstract Epidermal resident γδ T cells, or dendritic epidermal T cells (DETCs) in mice, are a unique and conserved population of γδ T cells enriched in the epidermis, where they serve as the regulators of immune responses and sense skin injury. Despite the great advances in the understanding of the development, homeostasis, and function of DETCs in the past decades, the origin and the underlying molecular mechanisms ...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2020 Category: Cytology Authors: Xu Y, Dimitrion P, Cvetkovski S, Zhou L, Mi QS Tags: Cell Mol Life Sci Source Type: research

PDCD4 limits prooncogenic neuregulin-ErbB signaling.
Abstract The neuregulins and their ErbB/HER receptors play essential roles in mammalian development and tissue homeostasis. In addition, deregulation of their function has been linked to the pathogenesis of diseases such as cancer or schizophrenia. These circumstances have stimulated research into the biology of this ligand-receptor system. Here we show the identification of programmed cell death protein-4 (PDCD4) as a novel neuregulin-ErbB signaling mediator. Phosphoproteomic analyses identified PDCD4 as protein whose phosphorylation increased in cells treated with neuregulin. Mutagenesis experiments defined seri...
Source: Cellular and Molecular Life Sciences : CMLS - August 16, 2020 Category: Cytology Authors: Montero JC, Pandiella A Tags: Cell Mol Life Sci Source Type: research

Extracellular vesicles and amyotrophic lateral sclerosis: from misfolded protein vehicles to promising clinical biomarkers.
Abstract Extracellular vesicles (EVs) are small reservoirs of different molecules and important mediators of cell-to-cell communication. As putative vehicles of misfolded protein propagation between cells, they have drawn substantial attention in the field of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Moreover, exosome-mediated non-coding RNA delivery may play a crucial role in ALS, given the relevance of RNA homeostasis in disease pathogenesis. Since EVs can enter the systemic circulation and are easily detectable in patients' biological fluids, they have generated broad interest b...
Source: Cellular and Molecular Life Sciences : CMLS - August 15, 2020 Category: Cytology Authors: Gagliardi D, Bresolin N, Comi GP, Corti S Tags: Cell Mol Life Sci Source Type: research

The ZIP6/ZIP10 heteromer is essential for the zinc-mediated trigger of mitosis.
Abstract Zinc has been known to be essential for cell division for over 40 years but the molecular pathways involved remain elusive. Cellular zinc import across biological membranes necessitates the help of zinc transporters such as the SLC39A family of ZIP transporters. We have discovered a molecular process that explains why zinc is required for cell division, involving two highly regulated zinc transporters, as a heteromer of ZIP6 and ZIP10, providing the means of cellular zinc entry at a specific time of the cell cycle that initiates a pathway resulting in the onset of mitosis. Crucially, when the zinc in...
Source: Cellular and Molecular Life Sciences : CMLS - August 13, 2020 Category: Cytology Authors: Nimmanon T, Ziliotto S, Ogle O, Burt A, Gee JMW, Andrews GK, Kille P, Hogstrand C, Maret W, Taylor KM Tags: Cell Mol Life Sci Source Type: research

Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length.
Abstract Maintaining the integrity of the mitotic spindle in metaphase is essential to ensure normal cell division. We show here that depletion of microtubule-associated protein ATIP3 reduces metaphase spindle length. Mass spectrometry analyses identified the microtubule minus-end depolymerizing kinesin Kif2A as an ATIP3 binding protein. We show that ATIP3 controls metaphase spindle length by interacting with Kif2A and its partner Dda3 in an Aurora kinase A-dependent manner. In the absence of ATIP3, Kif2A and Dda3 accumulate at spindle poles, which is consistent with reduced poleward microtubule flux and shortenin...
Source: Cellular and Molecular Life Sciences : CMLS - August 12, 2020 Category: Cytology Authors: Nehlig A, Seiler C, Steblyanko Y, Dingli F, Arras G, Loew D, Welburn J, Prigent C, Barisic M, Nahmias C Tags: Cell Mol Life Sci Source Type: research

Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization.
Abstract Poly(ADP-ribosyl)ation (PARylation) is an important post-translational modification mainly catalyzed by poly-ADP-ribose polymerase 1 (PARP1). In addition to having important roles in DNA damage detection and repair, it functions in gene expression regulation, especially at the posttranscriptional level. Embryonic lethal abnormal vision-like 1/human antigen R (ELAVL/HuR), a canonical 3' untranslated region AU-rich element-binding protein, is a crucial mRNA-stabilizing protein that protects target mRNAs from RNA-destabilizing protein- or microRNA-induced silencing complex (miRISC)-mediated degradation. Addi...
Source: Cellular and Molecular Life Sciences : CMLS - August 12, 2020 Category: Cytology Authors: Ke Y, Lv X, Fu X, Zhang J, Bohio AA, Zeng X, Hao W, Wang R, Boldogh I, Ba X Tags: Cell Mol Life Sci Source Type: research

Emerging roles of microRNAs and their implications in uveal melanoma.
Abstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults with an extremely high mortality rate. Genetic and epigenetic dysregulation contribute to the development of UM. Recent discoveries have revealed dysregulation of the expression levels of microRNAs (miRNAs) as one of the epigenetic mechanisms underlying UM tumorigenesis. Based on their roles, miRNAs are characterized as either oncogenic or tumor suppressive. This review focuses on the roles of miRNAs in UM tumorigenesis, diagnosis, and prognosis, as well as their therapeutic potentials. Particularly, the actions of collective miR...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2020 Category: Cytology Authors: Yang C, Wang Y, Hardy P Tags: Cell Mol Life Sci Source Type: research

Advances in research on ACE2 as a receptor for 2019-nCoV.
Abstract Currently, a novel coronavirus (SARS-CoV-2, also called 2019-nCoV) has triggered pandemic Coronavirus Disease 2019 (COVID-19), an acute infectious respiratory disease that first became epidemic in Wuhan (China) and is now spreading worldwide. Although 2019-nCoV and SARS-CoV are very similar viruses genomically and structurally, the huge number of severe cases and deaths now being caused by 2019-nCoV infections has understandably prompted intense research on the receptor used by it to enter human cells. Angiotensin converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediat...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2020 Category: Cytology Authors: Wu J, Deng W, Li S, Yang X Tags: Cell Mol Life Sci Source Type: research

ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.
mon L Abstract SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus that forms membraneless compartments called SAM68 Nuclear Bodies (SNBs). We found that intersectin 1 (ITSN1), a multidomain scaffold protein harboring five soluble SH3 domains, interacts with SAM68 proline-rich motifs (PRMs) surrounded by self-adhesive low complexity domains. While SAM68 is poorly soluble in vitro, the interaction of ITSN1 SH3 domains and mRNA with SAM68 enhances its solubility. In HeLa cells, the interaction between the first ITSN1 SH3 domain (SH3A) and P0, the N-terminal PRM of SAM68, induces the dissociat...
Source: Cellular and Molecular Life Sciences : CMLS - August 10, 2020 Category: Cytology Authors: Pankivskyi S, Pastré D, Steiner E, Joshi V, Rynditch A, Hamon L Tags: Cell Mol Life Sci Source Type: research

Defects of full-length dystrophin trigger retinal neuron damage and synapse alterations by disrupting functional autophagy.
Abstract Dystrophin (dys) mutations predispose Duchenne muscular disease (DMD) patients to brain and retinal complications. Although different dys variants, including long dys products, are expressed in the retina, their function is largely unknown. We investigated the putative role of full-length dystrophin in the homeostasis of neuro-retina and its impact on synapsis stabilization and cell fate. Retinas of mdx mice, the most used DMD model which does not express the 427-KDa dys protein (Dp427), showed overlapped cell death and impaired autophagy. Apoptotic neurons in the outer plexiform/inner nuclear layer and t...
Source: Cellular and Molecular Life Sciences : CMLS - August 3, 2020 Category: Cytology Authors: Catalani E, Bongiorni S, Taddei AR, Mezzetti M, Silvestri F, Coazzoli M, Zecchini S, Giovarelli M, Perrotta C, De Palma C, Clementi E, Ceci M, Prantera G, Cervia D Tags: Cell Mol Life Sci Source Type: research

An overview of signaling pathways regulating YAP/TAZ activity.
Abstract YAP and TAZ are ubiquitously expressed homologous proteins originally identified as penultimate effectors of the Hippo signaling pathway, which plays a key role in maintaining mammalian tissue/organ size. Presently, it is known that YAP/TAZ also interact with various non-Hippo signaling pathways, and have diverse roles in multiple biological processes, including cell proliferation, tissue regeneration, cell lineage fate determination, tumorigenesis, and mechanosensing. In this review, we first examine the various microenvironmental cues and signaling pathways that regulate YAP/TAZ activation, through the ...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2020 Category: Cytology Authors: Heng BC, Zhang X, Aubel D, Bai Y, Li X, Wei Y, Fussenegger M, Deng X Tags: Cell Mol Life Sci Source Type: research

Neuronal lineages derived from the nerve-associated Schwann cell precursors.
Abstract For a long time, neurogenic placodes and migratory neural crest cells were considered the immediate sources building neurons of peripheral nervous system. Recently, a number of discoveries revealed the existence of another progenitor type-a nerve-associated multipotent Schwann cell precursors (SCPs) building enteric and parasympathetic neurons as well as neuroendocrine chromaffin cells. SCPs are neural crest-derived and are similar to the crest cells by their markers and differentiation potential. Such similarities, but also considerable differences, raise many questions pertaining to the medical side, fu...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2020 Category: Cytology Authors: Kameneva P, Kastriti ME, Adameyko I Tags: Cell Mol Life Sci Source Type: research

NSun2 regulates aneurysm formation by promoting autotaxin expression and T cell recruitment.
g J Abstract Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell infiltration and aggravated by hyperhomocysteinemia (HHcy). It is unknown whether the homocysteine (Hcy)-activated RNA methyltransferase NOP2/Sun domain family member 2 (NSun2) is associated with AAA. Here, we found that NSun2 deficiency significantly attenuated elastase-induced and HHcy-aggravated murine AAA with decreased T cell infiltration in the vessel walls. T cell labeling and adoptive transfer experiments confirmed that NSun2 deficiency inhibited the chemotaxis of vessels to T cells. RNA sequencing of endothelial cells showe...
Source: Cellular and Molecular Life Sciences : CMLS - July 29, 2020 Category: Cytology Authors: Miao Y, Zhao Y, Han L, Ma X, Deng J, Yang J, Lü S, Shao F, Kong W, Wang W, Xu Q, Wang X, Feng J Tags: Cell Mol Life Sci Source Type: research

ORP/Osh mediate cross-talk between ER-plasma membrane contact site components and plasma membrane SNAREs.
d C Abstract OSBP-homologous proteins (ORPs, Oshp) are lipid binding/transfer proteins. Several ORP/Oshp localize to membrane contacts between the endoplasmic reticulum (ER) and the plasma membrane, where they mediate lipid transfer or regulate lipid-modifying enzymes. A common way in which they target contacts is by binding to the ER proteins, VAP/Scs2p, while the second membrane is targeted by other interactions with lipids or proteins.We have studied the cross-talk of secretory SNARE proteins and their regulators with ORP/Oshp and VAPA/Scs2p at ER-plasma membrane contact sites in yeast and murine primary neuron...
Source: Cellular and Molecular Life Sciences : CMLS - July 29, 2020 Category: Cytology Authors: Weber-Boyvat M, Trimbuch T, Shah S, Jäntti J, Olkkonen VM, Rosenmund C Tags: Cell Mol Life Sci Source Type: research

Maternal high protein-diet programs impairment of offspring's bone mass through miR-24-1-5p mediated targeting of SMAD5 in osteoblasts.
Abstract Maternal nutrition is crucial for the offspring's skeleton development and the onset of osteoporosis later in life. While maternal low protein diet has been shown to regulate bone mass negatively, the effect of a high protein diet (HP) remains unexplored. Here, we found that C57BL/6 mice fed with HP delivered offspring with decreased skeletal mineralization at birth and reduced bone mass throughout their life due to a decline in their osteoblast maturation. A small RNA sequencing study revealed that miR-24-1-5p was highly upregulated in HP group osteoblasts. Target prediction and validation studies identi...
Source: Cellular and Molecular Life Sciences : CMLS - July 29, 2020 Category: Cytology Authors: Ellur G, Sukhdeo SV, Khan MT, Sharan K Tags: Cell Mol Life Sci Source Type: research

The functional characteristics of optogenetic gene therapy for vision restoration.
We present an innovative combination of multi-electrode array recordings together with a complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally degenerated mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated using bipolar-cell targeted gene-delivery appro...
Source: Cellular and Molecular Life Sciences : CMLS - July 28, 2020 Category: Cytology Authors: Lindner M, Gilhooley MJ, Peirson SN, Hughes S, Hankins MW Tags: Cell Mol Life Sci Source Type: research

Polysialic acid and Siglec-E orchestrate negative feedback regulation of microglia activation.
Abstract Polysialic acid (polySia) emerges as a novel regulator of microglia activity. We recently identified polysialylated proteins in the Golgi compartment of murine microglia that are released in response to inflammatory stimulation. Since exogenously added polySia is able to attenuate the inflammatory response, we proposed that the release of polysialylated proteins constitutes a mechanism for negative feedback regulation of microglia activation. Here, we demonstrate that translocation of polySia from the Golgi to the cell surface can be induced by calcium depletion of the Golgi compartment and that polysialy...
Source: Cellular and Molecular Life Sciences : CMLS - July 27, 2020 Category: Cytology Authors: Thiesler H, Beimdiek J, Hildebrandt H Tags: Cell Mol Life Sci Source Type: research

Understanding COVID-19 via comparative analysis of dark proteomes of SARS-CoV-2, human SARS and bat SARS-like coronaviruses.
Abstract The recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 1.21 million cases of SARS-CoV-2 infection and more than 67,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. The World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted COVID-19 as a pandemic now...
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2020 Category: Cytology Authors: Giri R, Bhardwaj T, Shegane M, Gehi BR, Kumar P, Gadhave K, Oldfield CJ, Uversky VN Tags: Cell Mol Life Sci Source Type: research

The quest of cell surface markers for stem cell therapy.
Abstract Stem cells and their derivatives are novel pharmaceutics that have the potential for use as tissue replacement therapies. However, the heterogeneous characteristics of stem cell cultures have hindered their biomedical applications. In theory and practice, when cell type-specific or stage-specific cell surface proteins are targeted by unique antibodies, they become highly efficient in detecting and isolating specific cell populations. There is a growing demand to identify reliable and actionable cell surface markers that facilitate purification of particular cell types at specific developmental stages for ...
Source: Cellular and Molecular Life Sciences : CMLS - July 23, 2020 Category: Cytology Authors: Meyfour A, Pahlavan S, Mirzaei M, Krijgsveld J, Baharvand H, Salekdeh GH Tags: Cell Mol Life Sci Source Type: research

Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses.
so FJ Abstract Mesenchymal stem cells (MSC) are present in all organs and tissues. Several studies have shown the therapeutic potential effect of MSC or their derived products. However, the functional heterogeneity of MSC constitutes an important barrier for transferring these capabilities to the clinic. MSC heterogeneity depends on their origin (biological niche) or the conditions of potential donors (age, diseases or unknown factors). It is accepted that many culture conditions of the artificial niche to which they are subjected, such as O2 tension, substrate and extracellular matrix cues, inflammatory stimuli o...
Source: Cellular and Molecular Life Sciences : CMLS - July 21, 2020 Category: Cytology Authors: Costa LA, Eiro N, Fraile M, Gonzalez LO, Saá J, Garcia-Portabella P, Vega B, Schneider J, Vizoso FJ Tags: Cell Mol Life Sci Source Type: research

Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.
Abstract Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins. Here, using polyQ disease models, we aimed to demonstrate how miRNA-based gene expression regulation is dependent on target sequence features. We show that the silencing efficiency and...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2020 Category: Cytology Authors: Ciesiolka A, Stroynowska-Czerwinska A, Joachimiak P, Ciolak A, Kozlowska E, Michalak M, Dabrowska M, Olejniczak M, Raczynska KD, Zielinska D, Wozna-Wysocka M, Krzyzosiak WJ, Fiszer A Tags: Cell Mol Life Sci Source Type: research

Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance.
Abstract Histone deacetylases (HDACs) are conserved enzymes that regulate many cellular processes by catalyzing the removal of acetyl groups from lysine residues on histones and non-histone proteins. As appropriate for proteins that occupy such an essential biological role, HDAC activities and functions are in turn highly regulated. Overwhelming evidence suggests that the dysregulation of HDACs plays a major role in many human diseases. The regulation of HDACs is achieved by multiple different mechanisms, including posttranslational modifications. One of the most common posttranslational modifications on HDACs is ...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2020 Category: Cytology Authors: Bahl S, Seto E Tags: Cell Mol Life Sci Source Type: research

NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor.
NACHO and 14-3-3 promote expression of distinct subunit stoichiometries of the α4β2 acetylcholine receptor. Cell Mol Life Sci. 2020 Jul 16;: Authors: Mazzaferro S, Whiteman ST, Alcaino C, Beyder A, Sine SM Abstract Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of pentameric ligand-gated ion channels, and in neuronal tissues, are assembled from various types of α- and β-subunits. Furthermore, the subunits α4 and β2 assemble in two predominant stoichiometric forms, (α4)2(β2)3 and (α4)3(β2)2, forming receptors with dramatically...
Source: Cellular and Molecular Life Sciences : CMLS - July 15, 2020 Category: Cytology Authors: Mazzaferro S, Whiteman ST, Alcaino C, Beyder A, Sine SM Tags: Cell Mol Life Sci Source Type: research

Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation.
Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation. Cell Mol Life Sci. 2020 Jul 15;: Authors: Nam MH, Won W, Han KS, Lee CJ Abstract μ-opioid receptor (MOR) is a class of opioid receptors that is critical for analgesia, reward, and euphoria. MOR is distributed in various brain regions, including the hippocampus, where traditionally, it is believed to be localized mainly at the presynaptic terminals of the GABAergic inhibitory interneurons to exert a strong disinhibitory effect on excitatory pyramidal neurons. However, recent i...
Source: Cellular and Molecular Life Sciences : CMLS - July 14, 2020 Category: Cytology Authors: Nam MH, Won W, Han KS, Lee CJ Tags: Cell Mol Life Sci Source Type: research

Structure-function analysis of naturally occurring apolipoprotein A-I L144R, A164S and L178P mutants provides insight on their role on HDL levels and cardiovascular risk.
Abstract Naturally occurring point mutations in apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), may affect plasma HDL-cholesterol levels and cardiovascular risk. Here, we evaluated the effect of human apoA-I mutations L144R (associated with low HDL-cholesterol), L178P (associated with low HDL-cholesterol and increased cardiovascular risk) and A164S (associated with increased cardiovascular risk and mortality without low HDL-cholesterol) on the structural integrity and functions of lipid-free and lipoprotein-associated apoA-I in an effort to explain the phenotypes of subj...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2020 Category: Cytology Authors: Gkolfinopoulou C, Soukou F, Dafnis I, Kellici TF, Sanoudou D, Mavromoustakos T, Stratikos E, Chroni A Tags: Cell Mol Life Sci Source Type: research

Correction to: The effect of fornix deep brain stimulation in brain diseases.
Abstract After publication of the original article it came to the authors' attention that there was an error under the subheading Traumatic Brain Injury (TBI) as well as Table 1. PMID: 32661560 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2020 Category: Cytology Authors: Liu H, Temel Y, Boonstra J, Hescham S Tags: Cell Mol Life Sci Source Type: research

The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens.
Abstract Neutrophils are predominant immune cells that protect the human body against infections by deploying sophisticated antimicrobial strategies including phagocytosis of bacteria and neutrophil extracellular trap (NET) formation. Here, we provide an overview of the mechanisms by which neutrophils kill exogenous pathogens before we focus on one particular weapon in their arsenal: the generation of the oxidizing hypohalous acids HOCl, HOBr and HOSCN during the so-called oxidative burst by the enzyme myeloperoxidase. We look at the effects of these hypohalous acids on biological systems in general and proteins i...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2020 Category: Cytology Authors: Ulfig A, Leichert LI Tags: Cell Mol Life Sci Source Type: research

Metabolic crosstalk in the tumor microenvironment regulates antitumor immunosuppression and immunotherapy resisitance.
Abstract The successful treatment of human cancers by immunotherapy has been made possible by breakthroughs in the discovery of immune checkpoint regulators, including CTLA-4 and PD-1/PD-L1. However, the immunosuppressive effect of the tumor microenvironment still represents an important bottleneck that limits the success of immunotherapeutic approaches. The tumor microenvironment influences the metabolic crosstalk between tumor cells and tumor-infiltrating immune cells, creating competition for the utilization of nutrients and promoting immunosuppression. In addition, tumor-derived metabolites regulate the activa...
Source: Cellular and Molecular Life Sciences : CMLS - July 10, 2020 Category: Cytology Authors: Wei F, Wang D, Wei J, Tang N, Tang L, Xiong F, Guo C, Zhou M, Li X, Li G, Xiong W, Zhang S, Zeng Z Tags: Cell Mol Life Sci Source Type: research

Bassoon inhibits proteasome activity via interaction with PSMB4.
ova A Abstract Proteasomes are protein complexes that mediate controlled degradation of damaged or unneeded cellular proteins. In neurons, proteasome regulates synaptic function and its dysfunction has been linked to neurodegeneration and neuronal cell death. However, endogenous mechanisms controlling proteasomal activity are insufficiently understood. Here, we describe a novel interaction between presynaptic scaffolding protein bassoon and PSMB4, a β subunit of the 20S core proteasome. Expression of bassoon fragments that interact with PSMB4 in cell lines or in primary neurons attenuates all endopeptidase ac...
Source: Cellular and Molecular Life Sciences : CMLS - July 9, 2020 Category: Cytology Authors: Montenegro-Venegas C, Fienko S, Anni D, Pina-Fernández E, Frischknecht R, Fejtova A Tags: Cell Mol Life Sci Source Type: research

Macroglial diversity: white and grey areas and relevance to remyelination.
Abstract Macroglia, comprising astrocytes and oligodendroglial lineage cells, have long been regarded as uniform cell types of the central nervous system (CNS). Although regional morphological differences between these cell types were initially described after their identification a century ago, these differences were largely ignored. Recently, accumulating evidence suggests that macroglial cells form distinct populations throughout the CNS, based on both functional and morphological features. Moreover, with the use of refined techniques including single-cell and single-nucleus RNA sequencing, additional evidence ...
Source: Cellular and Molecular Life Sciences : CMLS - July 8, 2020 Category: Cytology Authors: Werkman IL, Lentferink DH, Baron W Tags: Cell Mol Life Sci Source Type: research

RBM38 in cancer: role and mechanism.
Abstract Cancer is the second leading cause of death globally. Abnormity in gene expression regulation characterizes the trajectory of tumor development and progression. RNA-binding proteins (RBPs) are widely dysregulated, and thus implicated, in numerous human cancers. RBPs mainly regulate gene expression post-transcriptionally, but emerging studies suggest that many RBPs can impact transcription by acting on chromatin as transcription factors (TFs) or cofactors. Here, we review the evidence that RBM38, an intensively studied RBP, frequently plays a tumor-suppressive role in multiple human cancer types. Genetic s...
Source: Cellular and Molecular Life Sciences : CMLS - July 7, 2020 Category: Cytology Authors: Zou C, Wan Y, He L, Zheng JH, Mei Y, Shi J, Zhang M, Dong Z, Zhang D Tags: Cell Mol Life Sci Source Type: research

Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.
Abstract AlkB homologs (ALKBH) are a family of specific demethylases that depend on Fe2+ and α-ketoglutarate to catalyze demethylation on different substrates, including ssDNA, dsDNA, mRNA, tRNA, and proteins. Previous studies have made great progress in determining the sequence, structure, and molecular mechanism of the ALKBH family. Here, we first review the multi-substrate selectivity of the ALKBH demethylase family from the perspective of sequence and structural evolution. The construction of the phylogenetic tree and the comparison of key loops and non-homologous domains indicate that the paralogs with ...
Source: Cellular and Molecular Life Sciences : CMLS - July 7, 2020 Category: Cytology Authors: Xu B, Liu D, Wang Z, Tian R, Zuo Y Tags: Cell Mol Life Sci Source Type: research

Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies.
Abstract The recent severe acute respiratory syndrome, known as Coronavirus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare a state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, the scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2020 Category: Cytology Authors: Mercurio I, Tragni V, Busto F, De Grassi A, Pierri CL Tags: Cell Mol Life Sci Source Type: research

Glial cells in Parkinson ´s disease: protective or deleterious?
Glial cells in Parkinson´s disease: protective or deleterious? Cell Mol Life Sci. 2020 Jul 02;: Authors: Domingues AV, Pereira IM, Vilaça-Faria H, Salgado AJ, Rodrigues AJ, Teixeira FG Abstract Glial cells have been identified more than 100 years ago, and are known to play a key role in the central nervous system (CNS) function. A recent piece of evidence is emerging showing that in addition to the capacity of CNS modulation and homeostasis, glial cells are also being looked like as a promising cell source not only to study CNS pathologies initiation and progression but also to the e...
Source: Cellular and Molecular Life Sciences : CMLS - July 1, 2020 Category: Cytology Authors: Domingues AV, Pereira IM, Vilaça-Faria H, Salgado AJ, Rodrigues AJ, Teixeira FG Tags: Cell Mol Life Sci Source Type: research