4TM-TRPM8 channels are new gatekeepers of the ER-mitochondria Ca2+ transfer
2018
Bidaux, Gabriel | Gordienko, Dmitri | Shapovalov, George | Farfariello, Valerio | Borowiec, Anne-Sophie | Iamshanova, Oksana | Lemonnier, Loic | Gueguinou, Maxime | Guibon, Roseline | Fromont, Gaelle | Paillard, Mélanie | Gouriou, Yves | Chouabe, Christophe | Dewailly, Etienne | Gkika, Dimitra | López-Alvarado, Pilar | Carlos Menéndez, J. | Héliot, Laurent | Slomianny, Christian | Prevarskaya, Natalia | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN) ; Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon) ; Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Laboratoire de Physiologie Cellulaire - U 1003 (PHYCELL) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille | Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM) ; Université de Lille-Centre National de la Recherche Scientifique (CNRS) | HCL Groupement Hospitalier Est | Bogomoletz Institute of Physiology ; Bogomoletz Institute of Physiology | Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-.2022] (GICC EA 7501) ; Université de Tours (UT) | Niche, Nutrition, Cancer et métabolisme oxydatif (N2Cox) ; Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM) | 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) | ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010)
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Show more [+] Less [-]English. Calcium (Ca2+) release from the endoplasmic reticulum plays an important role in many cell-fate defining cellular processes. Traditionally, this Ca2+ release was associated with the ER Ca2+ release channels, inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR). Lately, however, other calcium conductances have been found to be intracellularly localized and to participate in cell fate regulation. Nonetheless, molecular identity and functional properties of the ER Ca2+ release mechanisms associated with multiple diseases, e.g. prostate cancer, remain unknown. Here we identify a new family of transient receptor potential melastatine 8(TRPM8) channel isoforms as functional ER Ca2+ release channels expressed in mitochondria-associated ER membranes (MAMs). These TRPM8 isoforms exhibit an unconventional structure with 4 transmembrane domains (TMs) instead of 6 TMs characteristic of the TRP channel archetype. We show that these 4TM-TRPM8 isoforms form functional channels in the ER and participate in regulation of the steady-state Ca2+ concentration ([Ca2+]) in mitochondria and the ER. Thus, our study identifies 4TM-TRPM8 isoforms as ER Ca2+ release mechanism distinct from classical Ca(2+)release channels.
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