Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids
| Autor: | Yuri Panchin, Matthieu Flourakis, Fabien Vanden Abeele, Roman Skryma, Yaroslav M. Shuba, Alexander Zholos, Benjamin Beck, Stéphanie Thebault, Natalia Prevarskaya, Gabriel Bidaux |
|---|---|
| Přispěvatelé: | 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), INSERM the Ministère de l'Education Nationale La Ligue Nationale Contre le Cancer l'ARC the Nord/Pas-de- Calais region INTAS, Beck, Benjamin |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
TRPM Cation Channels
Stimulation [SDV.CAN]Life Sciences [q-bio]/Cancer Gating [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Endoplasmic Reticulum Ligands Biochemistry Phospholipases A Cell Line MESH: Lysophospholipids Group VI Phospholipases A2 03 medical and health sciences 0302 clinical medicine Phospholipase A2 [SDV.CAN] Life Sciences [q-bio]/Cancer MESH: Endoplasmic Reticulum TRPM8 MESH: Ligands Humans Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Ion channel 030304 developmental biology 0303 health sciences Phospholipase A MESH: Humans Cell Membrane MESH: TRPM Cation Channels Depolarization Cell Biology MESH: Ion Channel Gating Cell biology MESH: Cell Line Phospholipases A2 MESH: Calcium biology.protein MESH: Calcium Channels Calcium MESH: Phospholipases A Calcium Channels Signal transduction Lysophospholipids Ion Channel Gating 030217 neurology & neurosurgery MESH: Cell Membrane |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2006, 281 (52), pp.40174-82. ⟨10.1074/jbc.M605779200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M605779200⟩ |
| Popis: | TRPM8 represents an ion channel activated by cold temperatures and cooling agents, such as menthol, that underlies the cold-induced excitation of sensory neurons. Interestingly, the only human tissue outside the peripheral nervous system, in which the expression of TRPM8 transcripts has been detected at high levels, is the prostate, a tissue not exposed to any essential temperature variations. Here we show that the TRPM8 cloned from human prostate and heterologously expressed in HEK-293 cells is regulated by the Ca(2+)-independent phospholipase A(2) (iPLA(2)) signaling pathway with its end products, lysophospholipids (LPLs), acting as its endogenous ligands. LPLs induce prominent prolongation of TRPM8 channel openings that are hardly detectable with other stimuli (e.g. cold, menthol, and depolarization) and that account for more than 90% of the total channel open time. Down-regulation of iPLA(2) resulted in a strong inhibition of TRPM8-mediated functional responses and abolished channel activation. The action of LPLs on TRPM8 channels involved either changes in the local lipid bilayer tension or interaction with the critical determinant(s) in the transmembrane channel core. Based on this, we propose a novel concept of TRPM8 regulation with the involvement of iPLA(2) stimulation. This mechanism employs chemical rather than physical (temperature change) signaling and thus may be the main regulator of TRPM8 activation in organs not exposed to any essential temperature variations, as in the prostate gland. |
| Databáze: | OpenAIRE |
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