Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels. / Gopal, Sandeep; Søgaard, Pernille; Multhaupt, Hinke A B; Pataki, Csilla; Okina, Elena; Xian, Xiaojie; Pedersen, Mikael E; Stevens, Troy; Griesbeck, Oliver; Park, Pyong Woo; Pocock, Roger David John; Couchman, John R.
In: Journal of Cell Biology, Vol. 210, No. 7, 28.09.2015, p. 1199-211.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
VL - 210
SP - 1199
EP - 1211
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 7
ER -
ID: 166943442