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

Gopal, Sandeep LU orcid ; Søgaard, Pernille ; Multhaupt, Hinke A B ; Pataki, Csilla ; Okina, Elena ; Xian, Xiaojie LU ; Pedersen, Mikael E ; Stevens, Troy ; Griesbeck, Oliver and Park, Pyong Woo , et al. (2015) In Journal of Cell Biology 210(7). p.1199-1211
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Caenorhabditis elegans/genetics, Caenorhabditis elegans Proteins/genetics, Calcium/metabolism, Cell Line, Cytosol/metabolism, Humans, Mice, Mice, Mutant Strains, Protein Kinase C/genetics, Rats, Syndecan-4/genetics, TRPC Cation Channels/genetics
in
Journal of Cell Biology
volume
210
issue
7
pages
1199 - 1211
publisher
Rockefeller University Press
external identifiers
  • scopus:84957858954
  • pmid:26391658
ISSN
0021-9525
DOI
10.1083/jcb.201501060
language
English
LU publication?
no
additional info
© 2015 Gopal et al.
id
86b017ca-5565-4e1f-bd9a-50307cdf570e
date added to LUP
2021-10-25 13:16:06
date last changed
2024-06-16 22:35:07
@article{86b017ca-5565-4e1f-bd9a-50307cdf570e,
  abstract     = {{<p>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. </p>}},
  author       = {{Gopal, Sandeep and Søgaard, Pernille and Multhaupt, Hinke A B and Pataki, Csilla and Okina, Elena and Xian, Xiaojie and Pedersen, Mikael E and Stevens, Troy and Griesbeck, Oliver and Park, Pyong Woo and Pocock, Roger and Couchman, John R}},
  issn         = {{0021-9525}},
  keywords     = {{Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics; Calcium/metabolism; Cell Line; Cytosol/metabolism; Humans; Mice; Mice, Mutant Strains; Protein Kinase C/genetics; Rats; Syndecan-4/genetics; TRPC Cation Channels/genetics}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1199--1211}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Journal of Cell Biology}},
  title        = {{Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels}},
  url          = {{http://dx.doi.org/10.1083/jcb.201501060}},
  doi          = {{10.1083/jcb.201501060}},
  volume       = {{210}},
  year         = {{2015}},
}