Regulation of transient receptor potential melastatin 8 (TRPM8) channel activity by its short isoforms.

Gabriel Bidaux, Benjamin Beck, Alexander Zholos, Dimitri Gordienko, Loic Lemonnier, Matthieu Flourakis, Morad Roudbaraki, Anne-Sophie Borowiec, Jose Fernandez, Philippe Delcourt, Gilbert Lepage, Yaroslav Shuba, Roman Skryma, Natalia Prevarskaya

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2948-2962
Number of pages15
JournalJournal of Biological Chemistry
Volume287
Issue number5
Early online date28 Nov 2011
DOIs
Publication statusPublished - 27 Jan 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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