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

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

  • J Cell Biol. 2015 Jan 5;208(1):89-107. doi: 10.1083/jcb.201402076.
Dimitra Gkika 1,  Loic Lemonnier 2,  George Shapovalov 2,  Dmitri Gordienko 2,  Céline Poux 3,  Michela Bernardini 4,  Alexandre Bokhobza 2,  Gabriel Bidaux 5,  Cindy Degerny 6,  Kathye Verreman 6,  Basma Guarmit 7,  Mohamed Benahmed 7,  Yvan de Launoit 6,  Rene J M Bindels 8,  Alessandra Fiorio Pla 4,  Natalia Prevarskaya 2
Affiliations

Affiliations

  • 1 Inserm U1003, Equipe labellisée par la Ligue Nationale Contre le Cancer, Université des Sciences et Technologies de Lille (USTL), 59655 Villeneuve d'Ascq Cedex, France dimitra.gkika@univ-lille1.fr.
  • 2 Inserm U1003, Equipe labellisée par la Ligue Nationale Contre le Cancer, Université des Sciences et Technologies de Lille (USTL), 59655 Villeneuve d'Ascq Cedex, France.
  • 3 Centre national de la Recherche Scientifique (CNRS) UMR 8198 and Laboratoire de Génétique & Evolution des Populations Végétales (GEPV), Université des Sciences et Technologies de Lille (USTL), 59655 Villeneuve d'Ascq Cedex, France.
  • 4 Inserm U1003, Equipe labellisée par la Ligue Nationale Contre le Cancer, Université des Sciences et Technologies de Lille (USTL), 59655 Villeneuve d'Ascq Cedex, France Department of Life Science and Systems Biology, University of Torino, 10123 Torino, Italy.
  • 5 Laboratoire Biophotonique Cellulaire Fonctionnelle, Institut de Recherche Interdisciplinaire, USR3078 Centre National de la Recherche Scientifique, Parc scientifique de la Haute Borne, Villeneuve d'Ascq, F-59655 France.
  • 6 CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille-Nord de France, Institut Pasteur de Lille, 59019 Lille Cedex, France.
  • 7 Inserm, Institut National de la Santé et de la Recherche Médicale U895, Centre Méditerranéen de Médecine Moléculaire, Hôpitall'Archet, 06204 Nice, France.
  • 8 Department of Physiology, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, Netherlands.
PMID: 25559186 DOI: 10.1083/jcb.201402076
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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