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

First Author  Gopal S Year  2015
Journal  J Cell Biol Volume  210
Issue  7 Pages  1199-211
PubMed ID  26391658 Mgi Jnum  J:227549
Mgi Id  MGI:5701553 Doi  10.1083/jcb.201501060
Citation  Gopal S, et al. (2015) Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels. J Cell Biol 210(7):1199-211
abstractText  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.
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