VAMP7 regulates constitutive membrane incorporation of the cold-activated channel TRPM8

作者：Debapriya Ghosh, Sílvia Pinto, Lydia Danglot, Ine Vandewauw, Andrei Segal, Nele Van Ranst, Melissa Benoit, Annelies Janssens, Rudi Vennekens, Pieter Vanden Berghe, Thierry Galli, Joris Vriens, Thomas Voets · 发表于：Nature Communications · 年份：2016 · DOI：10.1038/ncomms10489 · 被引用次数：50 · 研究领域：Ion Channels and Receptors、Neurobiology and Insect Physiology Research、Ion channel regulation and function

The cation channel TRPM8 plays a central role in the somatosensory system, as a key sensor of innocuously cold temperatures and cooling agents. Although increased functional expression of TRPM8 has been implicated in various forms of pathological cold hypersensitivity, little is known about the cellular and molecular mechanisms that determine TRPM8 abundance at the plasma membrane. Here we demonstrate constitutive transport of TRPM8 towards the plasma membrane in atypical, non-acidic transport vesicles that contain lysosomal-associated membrane protein 1 (LAMP1), and provide evidence that vesicle-associated membrane protein 7 (VAMP7) mediates fusion of these vesicles with the plasma membrane. In line herewith, VAMP7-deficient mice exhibit reduced functional expression of TRPM8 in sensory neurons and concomitant deficits in cold avoidance and icilin-induced cold hypersensitivity. Our results uncover a cellular pathway that controls functional plasma membrane incorporation of a temperature-sensitive TRP channel, and thus regulates thermosensitivity in vivo.