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

Dimitra Gkika (1) , Loic Lemonnier (1) , George Shapovalov (1) , Dmitri Gordienko (1) , Céline Poux (2, 3) , Michela Bernardini (4, 1) , Alexandre Bokhobza (1) , Gabriel Bidaux (5) , Cindy Degerny (6) , Kathye Verreman (6) , Basma Guarmit (7) , Mohamed Benahmed (7) , Yvan de Launoit (6) , René J.M. Bindels (8) , Alessandra Fiorio Pla (1, 4) , Natalia Prevarskaya (1)

1 Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate
2 Evo-Eco-Paléo (EEP) - Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198
3 GEPV - Laboratoire de Génétique et Evolution des Populations Végétales
4 UNITO - Università degli studi di Torino = University of Turin
5 IRI - Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq]
6 M3T - Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161
7 C3M - Centre méditérannéen de médecine moléculaire
8 Radboud University Medical Center [Nijmegen]

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.

Mots clés: Abbreviations used in this paper: EAPA2; Experimental Autoimmune Prostatitis Antigen 2; FRET; Förster resonance energy transfer; HEK; human embryonic kidney; LNCaP; lymph node carcinoma of prostate; ML; maximum likelihood method; qPCR; quantitative real-time PCR; TCAF; TRP channel-associated factor; TCSPC; time-correlated single photon counting; TD FLIM; time-domain fluorescence lifetime imaging microscopy; TRP; transient receptor potential

Domaines: Génétique des populations [q-bio.PE]

Dimitra Gkika, Loic Lemonnier, George Shapovalov, Dmitri Gordienko, Céline Poux, et al.. TRP channel–associated factors are a novel protein family that regulates TRPM8 trafficking and activity. Journal of Cell Biology, 2015, 208 (1), pp.89-107. ⟨10.1083/jcb.201402076⟩. ⟨hal-01111024⟩