title: VAMP7 regulates constitutive membrane incorporation of the cold-activated channel TRPM8.
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.
authors: 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.
authors: Debapriya
authors: D
authors: Ghosh
authors: 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.
authors: Silvia
authors: S
authors: Pinto
authors: Institut Jacques Monod, CNRS UMR 7592, University of Paris Diderot, F-75013 Paris, France.|INSERM ERL U950, Membrane Traffic in Health &disease Group, F-75013 Paris, France.
authors: Lydia
authors: L
authors: Danglot
authors: 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.
authors: Ine
authors: I
authors: Vandewauw
authors: 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.
authors: Andrei
authors: A
authors: Segal
authors: 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.
authors: Nele
authors: N
authors: Van Ranst
authors: 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.
authors: Melissa
authors: M
authors: Benoit
authors: 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.
authors: Annelies
authors: A
authors: Janssens
authors: 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.
authors: Rudi
authors: http://orcid.org/0000-0002-2564-5150
authors: R
authors: Vennekens
authors: Laboratory for Enteric NeuroScience, Department of Clinical and Experimental Medicine, University of Leuven, B-3000 Leuven, Belgium.|Translational Research Centre for Gastrointestinal Disorders, KU Leuven, Herestraat 49 box 701, B-3000 Leuven, Belgium.
authors: Pieter
authors: P
authors: Vanden Berghe
authors: Institut Jacques Monod, CNRS UMR 7592, University of Paris Diderot, F-75013 Paris, France.|INSERM ERL U950, Membrane Traffic in Health &disease Group, F-75013 Paris, France.
authors: Thierry
authors: http://orcid.org/0000-0001-8514-7455
authors: T
authors: Galli
authors: 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.|Laboratory of Experimental Gynaecology, Department of Development and Regeneration, University of Leuven, Herestraat 49 box 611, B-3000 Leuven, Belgium.
authors: Joris
authors: J
authors: Vriens
authors: 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.
authors: Thomas
authors: http://orcid.org/0000-0001-5526-5821
authors: T
authors: Voets
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003080:Cold Temperature; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006941:Hyperesthesia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018408:Patch-Clamp Techniques; D011744:Pyrimidinones / Q000633:toxicity; D050683:R-SNARE Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D002118:Calcium; D051907:Lysosomal Membrane Proteins; D011744:Pyrimidinones; D050683:R-SNARE Proteins; D050053:TRPM Cation Channels; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C496927:Sybl1 protein, mouse; C492297:TRPM8 protein, mouse; C490483:icilin