title: TRP channel-associated factors are a novel protein family that regulates TRPM8 trafficking and activity.
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.
authors.affiliation: 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.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gkika
authors.affiliation: 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.
authors.forename: Loic
authors.initials: L
authors.lastname: Lemonnier
authors.affiliation: 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.
authors.forename: George
authors.initials: G
authors.lastname: Shapovalov
authors.affiliation: 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.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Gordienko
authors.affiliation: 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.
authors.forename: Céline
authors.initials: C
authors.lastname: Poux
authors.affiliation: 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.
authors.forename: Michela
authors.initials: M
authors.lastname: Bernardini
authors.affiliation: 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.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bokhobza
authors.affiliation: 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.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bidaux
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille-Nord de France, Institut Pasteur de Lille, 59019 Lille Cedex, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Degerny
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille-Nord de France, Institut Pasteur de Lille, 59019 Lille Cedex, France.
authors.forename: Kathye
authors.initials: K
authors.lastname: Verreman
authors.affiliation: Inserm, Institut National de la Santé et de la Recherche Médicale U895, Centre Méditerranéen de Médecine Moléculaire, Hôpitall'Archet, 06204 Nice, France.
authors.forename: Basma
authors.initials: B
authors.lastname: Guarmit
authors.affiliation: Inserm, Institut National de la Santé et de la Recherche Médicale U895, Centre Méditerranéen de Médecine Moléculaire, Hôpitall'Archet, 06204 Nice, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benahmed
authors.affiliation: CNRS UMR 8161, Institut de Biologie de Lille, Université de Lille-Nord de France, Institut Pasteur de Lille, 59019 Lille Cedex, France.
authors.forename: Yvan
authors.initials: Y
authors.lastname: de Launoit
authors.affiliation: Department of Physiology, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, Netherlands.
authors.forename: Rene J M
authors.initials: RJ
authors.lastname: Bindels
authors.affiliation: 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.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fiorio Pla
authors.affiliation: 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.
authors.forename: Natalia
authors.initials: N
authors.lastname: Prevarskaya
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C000595836:TCAF2 protein, human; D050053:TRPM Cation Channels; C000595834:TRPM8 channel-associated factor 1 protein, human; C425966:TRPM8 protein, human; C492297:TRPM8 protein, mouse