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

TY - JOUR

T1 - Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels

AU - Gopal, Sandeep

AU - Søgaard, Pernille

AU - Multhaupt, Hinke A B

AU - Pataki, Csilla

AU - Okina, Elena

AU - Xian, Xiaojie

AU - Pedersen, Mikael E

AU - Stevens, Troy

AU - Griesbeck, Oliver

AU - Park, Pyong Woo

AU - Pocock, Roger David John

AU - Couchman, John R

N1 - © 2015 Gopal et al.

PY - 2015/9/28

Y1 - 2015/9/28

N2 - 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.

AB - 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.

KW - Animals

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins

KW - Calcium

KW - Cell Line

KW - Cytosol

KW - Humans

KW - Mice

KW - Mice, Mutant Strains

KW - Protein Kinase C

KW - Rats

KW - Syndecan-4

KW - TRPC Cation Channels

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1083/jcb.201501060

DO - 10.1083/jcb.201501060

M3 - Journal article

C2 - 26391658

SN - 0021-9525

VL - 210

SP - 1199

EP - 1211

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 7

ER -