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J Cell Biol. 2015 Sep 28;210(7):1199-211. doi: 10.1083/jcb.201501060. Epub 2015 Sep 21.

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

Author information

1
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark.
2
Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark.
3
Department of Pharmacology, Center for Lung Biology, University of South Alabama, Mobile, AL 36688 Department of Medicine, Center for Lung Biology, University of South Alabama, Mobile, AL 36688.
4
Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
5
Division of Newborn Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115 Division of Respiratory Diseases, Children's Hospital, Harvard Medical School, Boston, MA 02115.
6
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark john.couchman@bric.ku.dk.

Abstract

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.

PMID:
26391658
PMCID:
PMC4586746
DOI:
10.1083/jcb.201501060
[Indexed for MEDLINE]
Free PMC Article

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