Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels
Research output: Contribution to journal › Journal article › Research › peer-review
Sandeep Gopal, Pernille Søgaard, Hinke A B Multhaupt, Csilla Pataki, Elena Okina, Xiaojie Xian, Mikael E Pedersen, Troy Stevens, Oliver Griesbeck, Pyong Woo Park, Roger David John Pocock, John R Couchman
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.
|Journal||Journal of Cell Biology|
|Number of pages||13|
|Publication status||Published - 28 Sep 2015|
- 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