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TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity.

Authors
  • Bokhobza Alexandre
  • Gkika, Dimitra
  • Lemonnier, Loic
  • Shapovalov, George
  • Gordienko, Dmitri
  • Poux, Céline
  • Bernardini, Michela
  • Bokhobza, Alexandre
  • Bidaux, Gabriel
  • Degerny, Cindy
  • Verreman, Kathye
  • Guarmit, Basma
  • Benahmed, Mohamed
  • de Launoit, Yvan
  • Bindels, Rene J M
  • Fiorio Pla, Alessandra
  • Prevarskaya, Natalia
Type
Published Article
Journal
The Journal of Cell Biology
Publisher
The Rockefeller University Press
Publication Date
Jan 05, 2015
Volume
208
Issue
1
Pages
89–107
Identifiers
DOI: 10.1083/jcb.201402076
PMID: 25559186
Source
Medline
License
Unknown

Abstract

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor-activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named "TRP channel-associated factors" (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.

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