title: Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2.
abstract: The transient receptor potential, sub-family Vanilloid (TRPV)(2) cation channel is activated in response to extreme temperature elevations in sensory neurons. However, TRPV2 is widely expressed in tissues with no sensory function, including cells of the immune system. Regulation of GRC, the murine homolog of TRPV2 has been studied in insulinoma cells and myocytes. GRC is activated in response to certain growth factors and neuropeptides, via a mechanism that involves regulated access of the channel to the plasma membrane. This is likely to be an important primary control mechanism for TRPV2 outside the CNS. Here, we report that a regulated trafficking step controls the access of TRPV2 to the cell surface in mast cells. In mast cells, elevations in cytosolic cAMP are sufficient to drive plasma membrane localization of TRPV2. We have previously proposed that the recombinase gene activator protein (RGA), a four-transmembrane domain, intracellular protein, associates with TRPV2 during the biosynthesis and early trafficking of the channel. We use a polyclonal antibody to RGA to confirm the formation of a physiological complex between RGA and TRPV2. Finally, we show that over-expression of the RGA protein potentiates the basal surface localization of TRPV2. We propose that trafficking and activation mechanisms intersect for TRPV2, and that cAMP mobilizing stimuli may regulate TRPV2 localization in non-sensory cells. RGA participates in the control of TRPV2 surface levels, and co-expression of RGA may be a key component of experimental systems that seek to study TRPV2 physiology.
authors.affiliation: Laboratory of Cell Biology and Immunology, Center for Biomedical Research at the Queen's Medical Center, Honolulu, HI 96813, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stokes
authors.forename: Clay
authors.initials: C
authors.lastname: Wakano
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Del Carmen
authors.forename: Murielle
authors.initials: M
authors.lastname: Koblan-Huberson
authors.forename: Helen
authors.initials: H
authors.lastname: Turner
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism*; D050916:TRPV Cation Channels
chemical_list: D000906:Antibodies; D007473:Ion Channels; D008565:Membrane Proteins; D011955:Receptors, Drug; C493780:Slc50a1 protein, mouse; D050916:TRPV Cation Channels; C476722:Trpv2 protein, rat; D000242:Cyclic AMP