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

Authors
Ghosh D, Pinto S, Danglot L, Vandewauw I et al

Lab
Laboratory of Ion Channel Research and TRP Channel Research Platform Leuven (TRPLe), Department of Cellular and Molecular Medicine, University of Leuven, Herestraat 49 box 802, B-3000 Leuven, Belgium.

Journal
Nature Communications

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.

BIOSEB Instruments Used:
Thermal Gradient Test (BIO-GRADIENT)