title: Agonist-dependent modulation of cell surface expression of the cold receptor TRPM8.
abstract: The spatial and temporal distribution of receptors constitutes an important mechanism for controlling the magnitude of cellular responses. Several members of the transient receptor potential (TRP) ion channel family can regulate their function by modulating their expression at the plasma membrane (PM) through rapid vesicular translocation and fusion. The mechanisms underlying this regulation are not completely understood, and the contribution of vesicular trafficking to physiological function is unknown. TRPM8 receptors are expressed in mammalian peripheral sensory neurons and are essential for the detection of cold temperatures. Previously, we showed that TRPM8-containing vesicles are segregated into three main pools, immobile at the PM, simple diffusive and corralled-hopping. Here, we show that channel expression at the PM is modulated by TRPM8 agonists in F11 and HEK293T cells. Our results support a model in which the activation of TRPM8 channels, located at the PM, induces a short-lived recruitment of a TRPM8-containing vesicular pool to the cell surface causing a transitory increase in the number of functional channels, affecting intrinsic properties of cold receptor responses. We further demonstrate the requirement of intact vesicular trafficking to support sustained cold responses in the skin of mice.
authors.affiliation: Instituto de Fisiología, Facultad de Medicina, Escuela de Graduados, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Toro
authors.affiliation: Klinik für Anästhesiologie, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany, and Institut für Physiologie und Pathophysiologie, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Eger
authors.affiliation: Instituto de Fisiología, Facultad de Medicina.
authors.forename: Luis
authors.initials: L
authors.lastname: Veliz
authors.affiliation: Instituto de Fisiología, Facultad de Medicina, Escuela de Graduados, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Sotelo-Hitschfeld
authors.affiliation: Instituto de Fisiología, Facultad de Medicina.
authors.forename: Deny
authors.initials: D
authors.lastname: Cabezas
authors.affiliation: Instituto de Bioquimica y Microbiologia, and.
authors.forename: Maite A
authors.initials: MA
authors.lastname: Castro
authors.affiliation: Klinik für Anästhesiologie, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany, and Institut für Physiologie und Pathophysiologie, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany sbrauchi@uach.cl katharina.zimmermann@fau.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Instituto de Fisiología, Facultad de Medicina, sbrauchi@uach.cl katharina.zimmermann@fau.de.
authors.forename: Sebastian
authors.identifier: http://orcid.org/0000-0002-8494-9912
authors.initials: S
authors.lastname: Brauchi
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D050053:TRPM Cation Channels / Q000819:agonists / Q000378:metabolism*
chemical_list: D009498:Neurotoxins; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D019274:Botulinum Toxins, Type A
keywords: Botulinum neurotoxin Type A (BoNTA); cold; diffusion; peripheral sensory neurons; skin nerve preparation; vesicle