Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels

Research output: Contribution to journalJournal articleResearchpeer-review

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-TRPC4 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-TRPC axis therefore fine tunes cytoskeletal organization and cell behavior.

Original languageEnglish
JournalJournal of Cell Biology
Issue number7
Pages (from-to)1199-211
Number of pages13
Publication statusPublished - 28 Sep 2015

    Research areas

  • Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Calcium, Cell Line, Cytosol, Humans, Mice, Mice, Mutant Strains, Protein Kinase C, Rats, Syndecan-4, TRPC Cation Channels, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

ID: 166943442