TRP channel–associated factors are a novel protein family that regulates TRPM8 trafficking and activity
- Others:
- Rôle des canaux ioniques membranaires et du calcium intracellulaire dans la physiopathologie de la prostate ; Université de Lille, Sciences et Technologies-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198 (Evo-Eco-Paléo (EEP)) ; Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Laboratoire de Génétique et Evolution des Populations Végétales ; Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)
- Università degli studi di Torino = University of Turin (UNITO)
- Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI) ; Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS)
- Mécanismes de tumorigenèse et thérapies ciblées ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Centre méditérannéen de médecine moléculaire (C3M) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 (M3T) ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Radboud University Medical Center [Nijmegen]
- This study was supported by grants from the French Ministère de l'Education Nationale and the Institut National de la Santé et de la Recherche Médicale. D. Gkika was supported by a long-term fellowship from the European Molecular Biology Organization (ALTF 161-2006) and the Institut National du Cancer Convention (07/3D1616/Pdoc-110-18/NG-NC). M. Bernardini was supported by the Vinci PhD fellowship of the Franco-Italian University (C3fr-64). D. Gordienko is supported by State Funds for Fundamental Research (F 46.2/001).
- The authors would like to thank Prof. Varda Rotter for kindly providing the human epithelial prostate cells, Ep156T; Prof Viana and Prof. Pardo for kindly providing with prostate cell lines and input for the analysis of endogenous TRPM8 function analysis; and Prof. Theodorus W.J. Gadella for the Original pmTurquoise2-N1, pmTurquoise2-C1, and pSYFP2-C1 vectors.
Description
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.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-01111024
- URN
- urn:oai:HAL:hal-01111024v1
- Origin repository
- UNICA