Journal of Cell Science (J Cell Sci )

Publisher: Company of Biologists

Description

Journal of Cell Science covers the complete range of topics in cell biology and is also of key interest to developmental biologists, molecular biologists and geneticists. It is one of the leading journals in the field, and its impact factor is rising steadily. Each issue includes research articles, as well as review articles commissioned from experts in particular fields, brief syntheses of important areas and topical comment. Journal of Cell Science is published twice monthly (24 issues/year).

  • Impact factor
    5.88
  • 5-year impact
    6.38
  • Cited half-life
    8.00
  • Immediacy index
    1.03
  • Eigenfactor
    0.11
  • Article influence
    2.89
  • Website
    Journal of Cell Science website
  • Other titles
    Journal of cell science (Online), Journal of cell science
  • ISSN
    1477-9137
  • OCLC
    37637228
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The neuronal function of Cys-loop neurotransmitter receptors is established; however, their role in non-neuronal cells is poorly defined. As brain tumors accumulate the neurotransmitter glycine, we studied expression and function of glycine receptors (GlyR) in glioma cells. Human brain tumor biopsies selectively expressed GlyR subunits with nuclear import signal (NLS, α1 and α3). The mouse glioma cell line GL261 expressed GlyR α1, and knock-down of α1 protein expression impaired self-renewal capacity and tumorigenicity of GL261 glioma cells as evidenced by the neurosphere assay and GL261 cell inoculation in vivo, respectively. We furthermore show that the pronounced tumorigenic effect of GlyR α1 relies on a new intracellular signaling function that depends on the NLS region in the large cytosolic loop and impacts on GL261 glioma cell gene regulation. Stable expression of GlyR α1 and α3 loops rescued self-renewal capacity of GlyR α1 knock-down cells, which demonstrates their functional equivalence. The new intracellular signaling function identified here goes beyond the well-established role of GlyRs as neuronal ligand-gated ion channels and defines NLS-containing GlyRs as novel potential targets for brain tumor therapies.
    Journal of Cell Science 07/2014;
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    ABSTRACT: Regulated, programmed cell death is crucial for all multicellular organisms. Cell death is essential in many processes, including tissue sculpting during embryogenesis, development of the immune system and destruction of damaged cells. The best-studied form of programmed cell death is apoptosis, a process that requires activation of caspase proteases. Recently it has been appreciated that various non-apoptotic forms of cell death also exist, such as necroptosis and pyroptosis. These non-apoptotic cell death modalities can be either triggered independently of apoptosis or are engaged should apoptosis fail to execute. In this Commentary, we discuss several regulated non-apoptotic forms of cell death including necroptosis, autophagic cell death, pyroptosis and caspase-independent cell death. We outline what we know about their mechanism, potential roles in vivo and define outstanding questions. Finally, we review data arguing that the means by which a cell dies actually matters, focusing our discussion on inflammatory aspects of cell death.
    Journal of Cell Science 05/2014; 127(Pt 10):2135-44.
  • Journal of Cell Science 05/2014; 127(Pt 10):2121.
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    ABSTRACT: The Src-Like Adaptor Protein (SLAP) is an adaptor protein sharing considerable structural homology with Src. SLAP is expressed in variety of cells regulating receptor tyrosine kinase signaling by direct association. In this report, we show that SLAP associates with both wild-type and oncogenic c-Kit (c-Kit-D816V). The association involves SLAP SH2 domain and receptor phosphotyrosine residues different from those mediating Src interaction. Association of SLAP triggers c-Kit ubiquitination which, in turn, is followed by receptor degradation. Although SLAP depletion potentiates c-Kit downstream signaling by stabilizing the receptor, it remains non-functional in c-Kit-D816V signaling. Ligand-stimulated c-Kit or c-Kit-D816V did not alter membrane localization of SLAP. Interestingly oncogenic c-Kit-D816V, but not wild-type c-Kit, phosphorylates SLAP on Y120, Y258 and Y273 residues. Physical interaction between c-Kit-D816V and SLAP is mandatory for the phosphorylation to take place. Although tyrosine phosphorylated SLAP does not affect c-Kit-D816V signaling, mutation of these tyrosine sites to phenylalanine can restore SLAP activity. Taken together the data demonstrate that SLAP negatively regulates wild-type c-Kit signaling, but not its oncogenic counterpart, indicating a possible mechanism by which the oncogenic c-Kit bypasses the normal cellular negative feedback control.
    Journal of Cell Science 05/2014; 127(Pt 10):2376.
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    ABSTRACT: mRNA localisation coupled to translational regulation provides an important means of dictating when and where proteins function in a variety of model systems. This mechanism is particularly relevant in polarised or migrating cells. Although many of the models for how this is achieved were first proposed over 20 years ago, some of the molecular details are still poorly understood. Nevertheless, advanced imaging, biochemical and computational approaches have started to shed light on the cis-acting localisation signals and trans-acting factors that dictate the final destination of localised transcripts. In this Cell Science at a Glance article and accompanying poster, we provide an overview of mRNA localisation, from transcription to degradation, focusing on the microtubule-dependent active transport and anchoring mechanism, which we will use to explain the general paradigm. However, it is clear that there are diverse ways in which mRNAs become localised and target protein expression, and we highlight some of the similarities and differences between these mechanisms.
    Journal of Cell Science 05/2014; 127(Pt 10):2127-33.
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    ABSTRACT: The M1 muscarinic acetylcholine receptor (M1-mAChR) is a G-protein-coupled membrane receptor that is activated by extracellular cholinergic stimuli. Recent investigations have revealed the intracellular localization of M1-mAChRs. In this study, we observed constitutive internalization of M1-mAChRs in mouse neuroblastoma N1E-115 cells without agonist stimulation. Constitutive internalization depends on dynamin, clathrin, and the adaptor protein-2 (AP-2) complex. A WXXI motif in the M1-mAChR C-terminus is essential for its constitutive internalization, since alanine mutations of W(442) or I(445) abolished constitutive internalization. This WXXI motif resembles YXXΦ, which is the canonical binding motif for the μ2 subunit of the AP-2 complex. The M1-mAChR C-terminal WXXI motif interacted with AP-2 μ2. W442A and I445A mutants of the M1-mAChR C-terminal sequence lost AP-2 μ2 binding activity, while the W442Y mutant bound more effectively than wild-type. Consistent with these results, W442A and I445A M1-mAChR mutants selectively localized to the cell surface. Conversely, the W442Y receptor mutant was found only at intracellular sites. Our data indicate that the cellular distribution of M1-mAChRs is governed by the C-terminal tryptophan-based motif that mediates constitutive internalization.
    Journal of Cell Science 05/2014;
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    ABSTRACT: Zinc (Zn(2+)) is an essential micronutrient and an important ionic signal, whose excess as well as scarcity are detrimental to cells. Free cytoplasmic Zn(2+) is controlled by a network of Zn(2+) transporters and chelating proteins. Recently, lysosomes became the focus of studies in Zn(2+) transport, as they were shown to play a role in zinc-induced toxicity by serving as Zn(2+) sinks that absorb Zn(2+) from the cytoplasm. Here we investigate the impact of the lysosomal Zn(2+) sink on the net cellular Zn(2+) distribution and its role in cell death. We found that lysosomes play a cytoprotective role during exposure to extracellular Zn(2+). Such a role required lysosomal acidification and exocytosis. Specifically, we found that the inhibition of lysosomal acidification using Bafilomycin A1 (Baf) lead to a redistribution of Zn(2+) pools, and increased apoptosis. Additionally, the inhibition of lysosomal exocytosis through knockdown (KD) of the lysosomal SNARE proteins VAMP7 and Synaptotagmin VII (SYT7) suppressed Zn(2+) secretion and VAMP7 KD cells had increased apoptosis. These data show that lysosomes play a central role in Zn(2+) handling, suggesting a novel Zn(2+) detoxification pathway.
    Journal of Cell Science 05/2014;
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    ABSTRACT: Dynamic modulation of the physical contacts between neighboring cells is integral to epithelial processes such as tissue repair and cancer dissemination. Induction of matrix metalloproteinase activity contributes to the disassembly of intercellular junctions and the degradation of the extracellular matrix, thus mitigating the physical constraint to cell movement. Using the cornea as a model, we show here that a carbohydrate-binding protein, galectin-3, promotes cell-cell detachment and redistribution of the tight junction protein occludin via its N-terminal polymerizing domain. Notably, we demonstrate that galectin-3 initiates cell-cell disassembly by inducing matrix metalloproteinase expression in a manner that is dependent on the interaction with and clustering of the matrix metalloproteinase inducer CD147 on the cell surface. Using galectin-3 knockout mice in an in vivo model of wound healing, we further show that increased synthesis of MMP9 at the leading edge of migrating epithelium is regulated by galectin-3. These findings establish a novel galectin-3-mediated regulatory mechanism for induction of metalloproteinase expression and disruption of cell-cell contacts required for cell motility in migrating epithelia.
    Journal of Cell Science 05/2014;
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    ABSTRACT: Analyses of apoptotic cell supernatants have helped identify many signals that modulate the states of activation and differentiation in the congeneric or other cells. However, the current knowledge about these soluble factors that are released during apoptosis is rather limited. Previous studies have shown that S5a/Angiocidin induced human acute monocytic leukemia cells (THP-1 cells) to differentiation into macrophages, but the cell surface receptor of S5a has not been identified. In this study we show that apoptotic THP-1 cells released endogenous S5a, and S5a bound with death receptor-6, which was identified as an orphan receptor, to induce THP-1 cells differentiation. Furthermore, we found NF-κB pathway was activated and the transcription factor WT1 and c-myb mediated THP-1 differentiation induced by S5a. And we also show that the differentiation was blocked after anti-DR6 antibody, DR6 siRNA, DR6-Fc, NF-κB inhibitor, or WT1 siRNA treatment. Our finding indicated that the interaction between cells can determine their destination. And we provided evidence for a functional interaction between S5a and DR6, which provides a novel target that can induce the differentiation of cancer cells especially for biotherapy of leukemia.
    Journal of Cell Science 05/2014;
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    ABSTRACT: Toll-like receptors (TLRs) and the receptors for interleukin (IL)-1, IL-18 and IL-33 are required for defence against microbial pathogens but, if hyper-activated or not switched off efficiently, can cause tissue damage and inflammatory and autoimmune diseases. Understanding how the checks and balances in the system are integrated to fight infection without the network operating out of control will be crucial for the development of improved drugs to treat these diseases in the future. In this Cell Science at a Glance article and the accompanying poster, I provide a brief overview of how one of these intricate networks is controlled by the interplay of protein phosphorylation and protein ubiquitylation events, and the mechanisms in myeloid cells that restrict and terminate its activation to prevent inflammatory and autoimmune diseases. Finally, I suggest a few protein kinases that have been neglected as drug targets, but whose therapeutic potential should be explored in the light of recent advances in our understanding of their roles in the innate immune system.
    Journal of Cell Science 05/2014;
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    ABSTRACT: By operating as both a subunit of the cadherin complex and a key component of Wnt signalling, β-catenin constitutes the lynchpin between cell:cell contact and transcriptional regulation of proliferation to co-ordinate epithelial tissue homeostasis and regeneration. Integration of multiple growth-regulatory inputs with β-catenin signalling has been observed in cancer-derived cells, yet the existence of pathway cross-talk in normal cells is unknown. Using a highly-regenerative normal human epithelial culture system that displays contact-inhibition, we demonstrate that the RTK-driven MAPK and Wnt/β-catenin signalling axes form a bidirectional positive-feedback loop to drive cellular proliferation. We show that β-catenin both drives and is regulated by proliferative signalling cues and its down-regulation coincides with the switch from proliferation to contact-inhibited quiescence. We reveal a novel contextual interrelationship whereby positive and negative feedback between three major signalling pathways EGFR/ERK, PI3K/AKT and Wnt/β-catenin enable autocrine-regulated tissue homeostasis as an emergent property of physical interactions between cells. Our work has direct implications for normal epithelial tissue homeostasis and provides insight as to how dysregulation of these pathways may drive excessive and sustained cellular growth in disease.
    Journal of Cell Science 05/2014;
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    ABSTRACT: The mechanisms underlying cell response to mechanical forces are critical for muscle development and functionality. We aim to determine whether mutations of the LMNA gene causing congenital muscular dystrophy impair the ability of muscle precursors to sense tissue stiffness and to respond to mechanical challenge. We found that LMNA-mutated myoblasts (LMNA) embedded in soft matrix did not align along the gel axis whereas control myoblasts did. LMNA myoblasts were unable to tune their cytoskeletal tension to the tissue stiffness as attested by inappropriate cell-matrix adhesion sites and cytoskeletal tension in soft versus rigid substrates or after mechanical challenge. Importantly, in soft 2D and/or static 3D conditions, LMNA myoblasts demonstrated enhanced activation of Yes-Associated Protein (YAP) signaling pathway that was paradoxically reduced after cyclic stretch. SiRNA-mediated downregulation of YAP reduced adhesion and actin stress fibers in LMNA myoblasts. This is the first demonstration that human myoblasts with LMNA mutations have mechanosensing defects through a YAP-dependent pathway. In addition, our data emphasize the crucial role of biophysical attributes of cellular microenvironment to the response of mechanosensing pathways in lamin A/C mutated myoblasts.
    Journal of Cell Science 05/2014;
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    ABSTRACT: In human cells appropriate mono-methylation of histone H4 lysine20 by PrSet7/SET8 is important for the correct transcription of specific genes, and timely progression through the cell cycle. Over-methylation appears to be prevented through the interaction of PrSet7 with PCNA, which targets PrSet7 destruction via the CRL4(cdt2) pathway, however the factors involved in positive regulation of its histone methylation remain undefined.Here we present biochemical and genetic evidence for a previously undocumented interaction between dPrSet7 and DNA polymerase-alpha in Drosophila. Depletion of the polymerase reduces H4K20 mono-methylation suggesting that it is required for the expression of dPrSet7 histone methylation activity. We also show that the interaction between PCNA and PrSet7 is conserved in Drosophila, but is only detectable in chromatin fractions. Consistent with this, S2 cells show a significant loss of chromatin bound dPrSet7 protein as S phase progresses.Based on these data we suggest that interaction with the DNA polymerase represents an important route for the expression of PrSet7 histone methylase activity, by allowing loading of dPrSet7 onto chromatin or its subsequent activation.
    Journal of Cell Science 05/2014;
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    ABSTRACT: BAG6 participates in protein quality control and we address its role during endoplasmic reticulum associated degradation (ERAD) using the polytopic membrane protein OpD. Both BAG6 knockdown and BAG6 overexpression delay OpD degradation, however, our data suggest these two perturbations are mechanistically distinct. Hence, BAG6 knockdown correlates with reduced OpD polyubiquitination, yet BAG6 overexpression increases polyubiquitinated OpD. The UBL- and BAG-domains of exogenous BAG6 are dispensable for OpD stabilisation and enhanced levels of polyubiquitinated OpD. Thus, whilst endogenous BAG6 normally promotes OpD degradation, exogenous BAG6 expression delays it; we speculate that over expressed BAG6 subunits may associate with the endogenous BAG6 complex, resulting in a dominant negative effect that inhibits its function. Interestingly cellular levels of BAG6 also correlate with total steady state polyubiquitination, with Rpn10 overexpression showing a similar effect. These findings suggest that perturbations to the levels of ubiquitin binding proteins can impact upon cellular ubiquitin homeostasis. We propose that exogenous BAG6 perturbs the function of the BAG6 complex at a stage beyond substrate recognition and polyubiquitination, most likely the BAG6-dependent delivery of OpD to the proteasome.
    Journal of Cell Science 05/2014;

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