Abstract：
:In culture, cell confluence generates signals that commit actively growing keratinocytes to exit the cell cycle and differentiate to form a stratified epithelium. Using a comparative proteomic approach, we studied this 'confluence switch' and identified a new pathway triggered by cell confluence that regulates basement membrane (BM) protein composition by suppressing the uPA-uPAR-plasmin pathway. Indeed, confluence triggers adherens junction maturation and enhances TGF-β and activin A activity, resulting in increased deposition of PAI-1 and perlecan in the BM. Extracellular matrix (ECM)-accumulated PAI-1 suppresses the uPA-uPAR-plasmin pathway and further enhances perlecan deposition by inhibiting its plasmin-dependent proteolysis. We show that perlecan deposition in the ECM strengthens cell adhesion, inhibits keratinocyte motility and promotes additional accumulation of PAI-1 in the ECM at confluence. In agreement, during wound-healing, perlecan concentrates at the wound-margin, where BM matures to stabilize keratinocyte adhesion. Our results demonstrate that confluence-dependent signaling orchestrates not only growth inhibition and differentiation, but also controls ECM proteolysis and BM formation. These data suggest that uncontrolled integration of confluence-dependent signaling, might favor skin disorders, including tumorigenesis, not only by promoting cell hyperproliferation, but also by altering protease activity and deposition of ECM components.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Botta A,Delteil F,Mettouchi A,Vieira A,Estrach S,Négroni L,Stefani C,Lemichez E,Meneguzzi G,Gagnoux-Palacios Ldoi
10.1242/jcs.096289subject
Has Abstractpub_date
2012-09-15 00:00:00pages
4241-52issue
Pt 18eissn
0021-9533issn
1477-9137pii
jcs.096289journal_volume
125pub_type
杂志文章abstract：:Pin1/Ess1p is a highly conserved WW domain-containing peptidyl-prolyl isomerase (PPIase); its WW domain binds specifically to phospho-Ser/Thr-Pro sequences and its catalytic domain isomerizes phospho-Ser/Thr-Pro bonds. Pin1 PPIase activity can alter protein conformation in a phosphorylation-dependent manner and/or pro...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:Paramecium tetraurelia is a unicellular organism that utilizes both axonemal and cytoplasmic dyneins. The highly conserved region containing the catalytic P-loop of the dynein heavy chain was amplified by RNA-directed polymerase chain reaction. Eight different P-loop-containing cDNA fragments were cloned. Southern hyb...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-04-01 00:00:00
abstract：:C-CAM (Cell-CAM 105) is a cell surface glycoprotein that is involved in cell-cell adhesion of rat hepatocytes in vitro. To elucidate the adhesion mechanism the binding properties of purified C-CAM were investigated. Using proteins immobilized on nitrocellulose it was found that radiolabeled C-CAM bound to C-CAM but no...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:Endo180 was previously characterized as a novel, cell type specific, recycling transmembrane glycoprotein. This manuscript describes the isolation of a full length human Endo180 cDNA clone which was shown to encode a fourth member of a family of proteins comprising the macrophage mannose receptor, the phospholipase A(...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-03-01 00:00:00
abstract：:BCL6 is a potent transcriptional repressor that plays important roles in germinal center formation, T helper cell differentiation and lymphomagenesis and regulates expression of several chemokine genes in macrophages. In a further investigation of its role in macrophages, we show that BCL6 inactivation in primary bone...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02314
更新日期：2005-05-01 00:00:00
abstract：:Mitochondria play essential roles in cellular energy processes, including ATP production, control of reactive oxygen species (ROS) and apoptosis. While mitochondrial function is regulated by the dynamics of fusion and fission, mitochondrial homeostasis remains incompletely understood. Recent studies implicate dynamin-...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.204537
更新日期：2017-07-15 00:00:00
abstract：:Start is the main decision point in the eukaryotic cell cycle at which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional programme through the inactivation of Start transcriptional repressors: the retinoblastoma family in mammals, or Whi5 and its recently identi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.251413
更新日期：2020-12-21 00:00:00
abstract：:We show that muscle satellite cells, traditionally considered as committed myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a mesenchymal repertoire extending beyond a mere myogenic potential. Mouse satellite cells from freshly isolated single myofibers, cultured individually in serum-ri...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01419
更新日期：2004-10-15 00:00:00
abstract：:During development, axons migrate long distances in responses to attractive or repulsive signals that are detected by their growth cones. One of these signals is mediated by netrin-1, a diffusible laminin-related molecule that both attracts and repels growth cones via interaction with its receptor DCC (deleted in colo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02296
更新日期：2005-04-15 00:00:00
abstract：:Laminins are heterotrimeric glycoproteins of the extracellular matrix that are secreted by epithelial cells and which are crucial for the normal structure and function of the basement membrane. We have generated a mouse harboring a conditional knockout of α3 laminin (Lama3(fl/fl)), one of the main laminin subunits in ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.080911
更新日期：2011-09-01 00:00:00
abstract：:When cultured cerebellar macroneurons develop attached to a laminin-containing substrate or after the acute addition of laminin to the tissue culture medium, there is an acceleration in the rate and extent of axonal elongation. Furthermore, laminin is capable of inducing axonal formation and microtubule stabilization ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:When tumour cells are fused with normal ones, malignancy is suppressed. It has been shown that this suppression is associated with the imposition on the hybrid cell of the terminal differentiation programme of the normal parent cell. We report here the consequences of imposing the synthesis of keratin 1 and keratin 10...
journal_title：Journal of cell science
pub_type：
doi：
更新日期：1996-09-01 00:00:00
abstract：:Mitogen-activated protein kinases (MAPKs) are conserved regulators of proliferation, differentiation and adaptation in eukaryotic cells. Their activity often involves changes in their subcellular localization, indicating an important role for these spatio-temporal dynamics in signal transmission. A striking model illu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.213462
更新日期：2018-05-04 00:00:00
abstract：:The contractile vacuole of the chloromonadophycean alga Vacuolaria virescens is a permanent structure that possesses a specialized membrane: subunits of this membrane have a diameter of 21-24 nm and in places are arranged in a regular hexagonal pattern. The lateral walls of these subunits form regularly spaced bristle...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-06-01 00:00:00
abstract：:The molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.044305
更新日期：2009-11-15 00:00:00
abstract：:Melanotransferrin (p97) is an iron-binding membrane glycoprotein with 40% homology to transferrin and lactoferrin. It was first identified on the basis of its high level of expression in melanoma cells, as compared to normal melanocytes. It is also present in many cultured cell types. In normal tissues, p97 is express...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes contain isoforms of two members of the cadherin superfamily of cell adhesion proteins, desmocollins (Dsc) and desmogleins (Dsg), but their combinatorial roles in desmosome assembly a...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.146316
更新日期：2014-05-15 00:00:00
abstract：:In many epithelial cells, epidermal growth factor (EGF) augments the epithelial-mesenchymal transition (EMT) that occurs when cells are treated with transforming growth factor β (TGFβ). We demonstrate that this augmentation requires activation of SH2 domain-containing phosphatase-2 (SHP2; also known as PTPN11), a prot...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.169599
更新日期：2015-11-01 00:00:00
abstract：:The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding pr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.064238
更新日期：2010-04-01 00:00:00
abstract：:Experimentally introduced tension on kinetochores and their centromeres has been shown to stabilize kinetochore attachment to microtubules, modify kinetochore directional instability, and regulate cell-cycle progression into anaphase. In mitosis, kinetochore tension and the stretch of centromere chromatin are produced...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:We have investigated the intracellular distribution of insoluble fibronectin in HeLa tumour cells. By indirect immunofluorescence microscopy fibronectin was detected in the nuclear region, but not in the region of the cell surface. Isolated nuclei and isolated nuclear matrices also stained for fibronectin. By quantita...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:Mouse oocytes are induced by cytochalasin B to undergo 'pseudo-cleavage' in vitro into 2 equally sized and separable compartments. This response to the drug is dependent upon the meiotic state of the oocytes, as well as upon the presence of an intact zona pellucida. The resulting 2 cellular compartments can be complet...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
abstract：:Vascular endothelial (VE)-cadherin is the endothelium-specific member of the cadherin family of homotypic cell adhesion molecules. VE-cadherin, but not the cell adhesion molecule platelet/endothelial cell adhesion molecule (PECAM-1), markedly colocalizes with actin stress fibers at cell-cell junctions between human um...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
abstract：:Neutrophils enter sites of inflammation by crossing the endothelial lining of the blood vessel wall. VE-cadherin is an endothelial specific, homophilic adhesion molecule located at the lateral cell surface. We have generated a monoclonal antibody against mouse VE-cadherin which inhibits electrical resistance of endoth...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:The effect of glycosaminoglycans on the invasion of choroid fibroblasts into type I collagen gels was studied. Both hyaluronate and chondroitin sulphate, when incorporated into the gel, facilitated invasion of the collagen matrix, although hyaluronate was considerably more effective. Hyaluronate-induced fibroblast inv...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the express...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.141556
更新日期：2014-08-01 00:00:00
abstract：:The effects of hyaluronate on the morphology, motile and social behaviour of embryonic chick heart fibroblasts were examined in the presence or absence of hyaluronate binding proteins (HABP). HABP were inserted onto fibroblasts after treating cells with 0.2 M-urea. Such treatment increased the binding of [125I]HABP to...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:In our previous experiments with linear strips of adhesive substrate, we found that elongated cultured fibroblasts preserve their length regardless of cell width and the number of cytoplasmic processes. This constancy of length was called 'length control'. In contrast to fibroblasts, single cultured epitheliocytes hav...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01054
更新日期：2004-04-15 00:00:00
abstract：:Members of the PAR-1/MARK kinase family play critical roles in polarity and cell cycle control and are regulated by 14-3-3 scaffolding proteins, as well as the LKB1 tumour suppressor kinase and atypical protein kinase C (PKC). In this study, we initially investigated the mechanism underlying the interaction of mammali...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03097
更新日期：2006-10-01 00:00:00
abstract：:A key signaling event that is responsible for gradient sensing in eukaryotic cell chemotaxis is a phosphatidylinositol (PtdIns) lipid reaction system. The self-organization activity of this PtdIns lipid system induces an inherent polarity, even in the absence of an external chemoattractant gradient, by producing a loc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.108373
更新日期：2012-11-01 00:00:00
