title: Regulation of activity of transient receptor potential melastatin 8 (TRPM8) channel by its short isoforms.
abstract: One important mechanism of the regulation of membrane ion channels involves their nonfunctional isoforms generated by alternative splicing. However, knowledge of such isoforms for the members of the transient receptor potential (TRP) superfamily of ion channels remains quite limited. This study focuses on the TRPM8, which functions as a cold receptor in sensory neurons but is also expressed in tissues not exposed to ambient temperatures, as well as in cancer tissues. We report the cloning from prostate cancer cells of new short splice variants of TRPM8, termed short TRPM8α and short TRPM8β. Our results show that both variants are in a closed configuration with the C-terminal tail of the full-length TRPM8 channel, resulting in stabilization of its closed state and thus reducing both its cold sensitivity and activity. Our findings therefore uncover a new mode of regulation of the TRPM8 channel by its splice variants.
authors: INSERM U1003, Equipe Labellisée par la Ligue Nationale contre le Cancer and the Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France. gabriel.bidaux@univ-lille1.fr
authors: Gabriel
authors: G
authors: Bidaux
authors: Benjamin
authors: B
authors: Beck
authors: Alexander
authors: A
authors: Zholos
authors: Dmitri
authors: D
authors: Gordienko
authors: Loic
authors: L
authors: Lemonnier
authors: Matthieu
authors: M
authors: Flourakis
authors: Morad
authors: M
authors: Roudbaraki
authors: Anne-Sophie
authors: AS
authors: Borowiec
authors: José
authors: J
authors: Fernández
authors: Philippe
authors: P
authors: Delcourt
authors: Gilbert
authors: G
authors: Lepage
authors: Yaroslav
authors: Y
authors: Shuba
authors: Roman
authors: R
authors: Skryma
authors: Natalia
authors: N
authors: Prevarskaya
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human