TY - JOUR
T1 - Regulation of transient receptor potential melastatin 8 (TRPM8) channel activity by its short isoforms.
AU - Bidaux, Gabriel
AU - Beck, Benjamin
AU - Zholos, Alexander
AU - Gordienko, Dimitri
AU - Lemonnier, Loic
AU - Flourakis, Matthieu
AU - Roudbaraki, Morad
AU - Borowiec, Anne-Sophie
AU - Fernandez, Jose
AU - Delcourt, Philippe
AU - Lepage, Gilbert
AU - Shuba, Yaroslav
AU - Skryma, Roman
AU - Prevarskaya, Natalia
PY - 2012/1/27
Y1 - 2012/1/27
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M111.270256
DO - 10.1074/jbc.M111.270256
M3 - Article
C2 - 22128173
VL - 287
SP - 2948
EP - 2962
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -
