Journal of Cell Science (J Cell Sci )

Publisher: Company of Biologists


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 5.33

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  • Website
    Journal of Cell Science website
  • Other titles
    Journal of cell science (Online), Journal of cell science
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    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasma membrane lipid asymmetry is important for various membrane-associated functions and is regulated by membrane proteins termed flippases and floppases. The Rim101 pathway senses altered lipid asymmetry in the yeast plasma membrane. The mutant lem3 Δ cells, in which lipid asymmetry is disturbed owing to the inactivation of the plasma membrane flippases, showed a severe growth defect when the Rim101 pathway was impaired. To identify factors involved in the Rim101-pathway-dependent adaptation to altered lipid asymmetry, we performed DNA microarray analysis and found that Opt2 induced by the Rim101 pathway plays an important role in the adaptation to altered lipid asymmetry. Biochemical investigation of Opt2 revealed its localization to the plasma membrane and the Golgi, and provided several lines of evidence for the Opt2-mediated exposure of phospholipids. In addition, Opt2 was found to be required for the maintenance of vacuolar morphology and polarized cell growth. These results suggest that Opt2 is a novel factor involved in cell homeostasis by regulating lipid asymmetry.
    Journal of Cell Science 01/2015; 128(1):61-69.
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    ABSTRACT: F-BAR proteins are prime candidates to regulate membrane curvature and dynamics during different developmental processes. Here, we analyzed nostrin (nost), a novel Drosophila F-BAR protein related to Cip4. Genetic analyses revealed a strong synergism between nost and cip4 functions. While single mutant flies are viable and fertile, combined loss of nost and cip4 results in reduced viability and fertility. Double mutant escaper flies show enhanced wing polarization defects and females exhibit strong egg chamber encapsulation defects. Live-imaging analysis suggests that the observed phenotypes are caused by an impaired E-cadherin membrane turnover. Simultaneous knock-down of Cip4 and Nostrin strongly increases the formation of tubular E-cadherin vesicles at adherens junctions. Cip4 and Nostrin localize at distinct membrane subdomains. Both proteins prefer similar membrane curvatures but seem to form different membrane coats and do not heterooligomerize. Our data suggest an important synergistic function of both F-BAR proteins in membrane dynamics. We propose a cooperative recruitment model in which first Cip4 promotes membrane invagination and early actin-based endosomal motility while Nostrin makes contact with microtubules through the kinesin Khc-73 for trafficking of recycling endosomes.
    Journal of Cell Science 11/2014;
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    ABSTRACT: The mechanism that coordinates different adhesion receptors is poorly understood. We investigated this mechanism by focusing on the nectin-2 and E-cadherin adherens junction receptors. Cadherin is not required for the basic process of nectin junction formation since nectin-2 forms junctions in cadherin-deficient A431D cells. Formation of nectin junctions in these cells, however, becomes regulated by cadherin as soon as E-cadherin is reconstituted. E-cadherin recruits nectin-2 into adherens junctions, where both proteins form distinct but tightly associated clusters. Live-cell imaging showed that the appearance of cadherin clusters often precedes that of nectin clusters at sites of junction assembly. Inactivation of cadherin clustering by different strategies concomitantly suppresses the formation of nectin clusters. Furthermore, cadherin significantly increases the stability of nectin clusters, thereby making them resistant to the BC-12 antibody, which targets the nectin-2 adhesion interface. By testing different cadherin-α-catenin chimeras, we showed that the recruitment of nectin into chimera junctions is mediated by the actin-binding domain of α-catenin. Our data suggests that cadherin regulates-assembly of nectin junctions through α-catenin-induced remodeling of the actin cytoskeleton around the cadherin clusters.
    Journal of Cell Science 11/2014;
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    ABSTRACT: Host cell invasion by Trypanosoma cruzi shares mechanistic elements with plasma membrane injury and repair. Both processes require Ca2+-triggered exocytosis of lysosomes, exocytosis of acid sphingomyelinase, and formation of ceramide-enriched endocytic compartments. T. cruzi invades at peripheral sites, suggesting a need for spatial regulation of membrane traffic. Here we show that Exo70 and Sec8, components of the exocyst complex, accumulate in nascent T. cruzi vacuoles and at sites of mechanical wounding. Exo70 or Sec8 depletion inhibits T. cruzi invasion and Ca2+-dependent resealing of mechanical wounds, but does not affect repair of smaller lesions caused by pore-forming toxins. Thus, T. cruzi invasion and mechanical lesion repair share a unique requirement for the exocyst, consistent with a dependence on targeted membrane delivery.
    Journal of Cell Science 11/2014;
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    ABSTRACT: Ca2+-dependent regulation of fusion pore dilation/closure is a key mechanism determining the output of cellular secretion. We have recently described „fusion-activated“ Ca2+-entry (FACE) following exocytosis of lamellar bodies (LBs) in alveolar type II cells. FACE regulates fusion pore expansion and facilitates secretion. Yet, mechanisms linking this locally restricted Ca2+ signal and fusion pore expansion were still elusive. Here we demonstrate that synaptotagmin-7 (syt-7) is expressed on LBs and links FACE and fusion pore dilation. We directly assessed dynamic changes in fusion pore diameters analysing diffusion of fluorophores across fusion pores. Expressing wt or mutant syt-7 with impaired Ca2+-binding to the C2 domains revealed that binding of Ca2+ to the C2A domain facilitates FACE-induced pore dilation, likely inhibiting translocation of complexin-2 to fused vesicles. However, the C2A domain hampered Ca2+-dependent exocytosis of LBs. These findings support that syt-7 modulates fusion pore expansion in large secretory organelles and extend our picture that LBs contain the necessary molecular inventory to facilitate secretion during the exocytic post-fusion phase. Moreover, regulating syt-7 levels on LBs appears essential to not impede exocytosis during the pre-fusion phase.
    Journal of Cell Science 10/2014;
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    ABSTRACT: Chronic vascular inflammation is driven by interactions between activated leukocytes and the endothelium. Leukocyte β2-integrins bind to endothelial ICAM-1 (InterCellular Adhesion Molecule-1), which allows leukocyte spreading, crawling and transendothelial migration. Leukocytes scan the vascular endothelium for permissive sites to transmigrate suggestive for apical membrane heterogeneity within the endothelium. However, the molecular basis for this heterogeneity is unknown. Leukocyte adhesion induces ICAM-1 clustering which promotes its association to the actin-binding proteins FilaminB, α-Actinin-4 and Cortactin. We show that these endothelial proteins differentially control adhesion, spreading and transmigration of neutrophils. Loss of FilaminB, α-Actinin-4 and Cortactin revealed adapter-specific effects on a nuclear-to-peripheral gradient of endothelial cell stiffness. Conversely, increasing endothelial cell stiffness stimulates ICAM-1 function. We identify endothelial α-Actinin-4 as a key regulator of endothelial cell stiffness and of ICAM-1-mediated neutrophil transmigration. Finally, we found that the endothelial lining of human and murine atherosclerotic plaques shows elevated levels of α-Actinin-4. These results identify endothelial cell stiffness as an important regulator of endothelial surface heterogeneity and of ICAM-1 function which in turn controls adhesion and transmigration of neutrophils.
    Journal of Cell Science 10/2014; 127(20):4470-82.
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    ABSTRACT: Recent work has demonstrated that the receptor-mediated signaling system in chemotactic amoeboid cells shows typical properties of an excitable system. Here, we delivered spatially confined stimuli of the chemoattractant cAMP to the membrane of differentiated Dictyostelium discoideum cells to investigate whether localized receptor stimuli can induce the spreading of excitable waves in the G-protein dependent signal transduction system. By imaging the spatiotemporal dynamics of fluorescent markers for PIP3, PTEN, and filamentous actin, we observed that the activity of the signaling pathway remained spatially confined to the stimulated membrane region. Neighboring parts of the membrane were not excited and no receptor-initiated spatial spreading of excitation waves was observed. To generate localized cAMP stimuli, either particles that carried covalently bound cAMP molecules on their surface were brought into contact with the cell, or a patch of the cell membrane was aspirated into a glass micropipette to shield this patch against freely diffusing cAMP molecules in the surrounding medium. Additionally, also the binding site of the cAMP receptor was probed with different surface-immobilized cAMP molecules, confirming results from earlier ligand binding studies.
    Journal of Cell Science 10/2014; Advance Online Article.
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    ABSTRACT: Pregnancy-associated plasma protein-A2 (PAPP-A2, pappalysin-2) is a large metalloproteinase, known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in chordamesoderm, notochord, and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2 knockdown embryos display broadened axial mesoderm, notochord bends, and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor binding protein-3 (Igfbp-3) and Bmp signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Concordantly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.
    Journal of Cell Science 09/2014;
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    ABSTRACT: The membrane and actin cortex of a motile cell can autonomously differentiate into two states, one typical of the front, the other of the tail. On the substrate-attached surface of Dictyostelium cells, dynamic patterns of front-like and tail-like states are generated that are best suited to monitor transitions between these states. To image large-scale pattern dynamics independent of boundary effects, we produced giant cells by electric-pulse induced cell fusion. In these cells actin waves are coupled to the front and back bands of PIP3-rich bands that have a finite width. that are flanked at their front and back by an actin wave These composite waves propagate across the plasma membrane of the giant cells with undiminished velocity. After any disturbance, the bands of PIP3 are characterized by an return to their intrinsic width. to which they return after any disturbance Upon collision, the waves locally annihilate each other and change direction; at the cell border they are either extinguished or reflected. Accordingly, expanding areas of progressing PIP3 synthesis become unstable beyond a critical radius, their center switching from a front-like to a tail-like state. Our data suggest that PIP3 patterns in normal-sized cells are segments of the self-organizing patterns that evolve in giant cells.
    Journal of Cell Science 08/2014;
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    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.
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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 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.
  • Journal of Cell Science 05/2014; 127(Pt 10):2121.
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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;