Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

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

Authors: 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

Journal, date & volume: Nat Commun, 2016 , 7, 10489

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26843440

Abstract
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.