title: Cell-extracellular matrix and cell-cell adhesion are linked by syndecan-4.
abstract: Cell-extracellular matrix (ECM) and cell-cell junctions that employ microfilaments are sites of tension. They are important for tissue repair, morphogenetic movements and can be emblematic of matrix contraction in fibrotic disease and the stroma of solid tumors. One cell surface receptor, syndecan-4, has been shown to regulate focal adhesions, junctions that form at the ends of microfilament bundles in response to matrix components such as fibronectin. Recently it has been shown that signaling emanating from this proteoglycan receptor includes regulation of Rho family GTPases and cytosolic calcium. While it is known that cell-ECM and cell-cell junctions may be linked, possible roles for syndecans in this process are not understood. Here we show that wild type primary fibroblasts and those lacking syndecan-4 utilize different cadherins in their adherens junctions and that tension is a major factor in this differential response. This corresponds to the reduced ability of fibroblasts lacking syndecan-4 to exert tension on the ECM and we now show that this may extend to reduced tension in cell-cell adhesion.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark; Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Dept. of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Hinke A B
authors.initials: HAB
authors.lastname: Multhaupt
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Dept. of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Pocock
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: john.couchman@bric.ku.dk.
authors.forename: John R
authors.initials: JR
authors.lastname: Couchman
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051379:Mice; D000075983:Nectins / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053671:Syndecan-4 / Q000172:deficiency / Q000235:genetics*; D016596:Vinculin / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; C000619016:Nectin2 protein, mouse; D000075983:Nectins; D051419:Paxillin; D020033:Protein Isoforms; C496062:Pxn protein, mouse; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016596:Vinculin; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D000095002:Delta Catenin
keywords: Adherens junction; Cadherin; Focal adhesion; Heparan sulfate; Proteoglycan