{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:42:07Z","timestamp":1790790127783,"version":"4.1.0"},"reference-count":62,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,28]]},"abstract":"<jats:p>Transmembrane heparan sulfate proteoglycans regulate multiple aspects of cell behavior, but the molecular basis of their signaling is unresolved. The major family of transmembrane proteoglycans is the syndecans, present in virtually all nucleated cells, but with mostly unknown functions. Here, we show that syndecans regulate transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7 with subsequent control of the cytoskeleton and the myofibroblast phenotype. In epidermal keratinocytes a syndecan\u2013TRPC4 complex controls adhesion, adherens junction composition, and early differentiation in vivo and in vitro. In Caenorhabditis elegans, the TRPC orthologues TRP-1 and -2 genetically complement the loss of syndecan by suppressing neuronal guidance and locomotory defects related to increases in neuronal calcium levels. The widespread and conserved syndecan\u2013TRPC axis therefore fine tunes cytoskeletal organization and cell behavior.<\/jats:p>","DOI":"10.1083\/jcb.201501060","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T21:44:33Z","timestamp":1442871873000},"page":"1199-1211","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":82,"title":["Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels"],"prefix":"10.1083","volume":"210","author":[{"given":"Sandeep","family":"Gopal","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"S\u00f8gaard","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinke A.B.","family":"Multhaupt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Pataki","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Okina","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Xian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael E.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Lung Biology, University of South Alabama, Mobile, AL 36688 3"},{"name":"Department of Medicine, Center for Lung Biology, University of South Alabama, Mobile, AL 36688 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Griesbeck","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Neurobiology, 82152 Martinsried, Germany 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pyong Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115 6"},{"name":"Division of Respiratory Diseases, Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Pocock","sequence":"additional","affiliation":[{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Couchman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 1"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2015,9,21]]},"reference":[{"key":"2023072308032666100_bib1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/77108","article-title":"Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice","volume":"25","author":"Alexander","year":"2000","journal-title":"Nat. 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