title: Rapid vesicular translocation and insertion of TRP channels.
abstract: The broadly expressed transient receptor potential (TRP) family of ion channels are permeant to cations, most resulting in increased intracellular calcium. However, their regulation and gating is not well understood. Here, we report that growth factor stimulation initiates the rapid translocation of the transient receptor potential ion channel, TRPC5, from vesicles held in reserve just under the plasma membrane. This process, which we term 'rapid vesicular insertion of TRP' (RiVIT), dramatically increases membrane-associated TRPC5 channels and functional TRPC5 current, resulting in tight spatial-temporal control of these Ca(2+)-permeant nonselective channels. Epidermal growth factor (EGF)-induced incorporation of functional TRP channels requires phosphatidylinositide 3-kinase (PI(3)K), the Rho GTPase Rac1 and phosphatidylinositol 4-phosphate 5-kinase (PIP(5)K alpha). The increase in TRPC5 availability affects neurite extension rates in cultured hippocampal neurons, and may be a general mechanism for initiating Ca(2+) influx and cell morphological changes in response to stimuli.
authors.affiliation: Howard Hughes Medical Institute, Cardiovascular Department, Children's Hospital and Harvard Medical School, Enders 1309 320 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Vassilios J
authors.initials: VJ
authors.lastname: Bezzerides
authors.forename: I Scott
authors.initials: IS
authors.lastname: Ramsey
authors.forename: Suhas
authors.initials: S
authors.lastname: Kotecha
authors.forename: Anna
authors.initials: A
authors.lastname: Greka
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D027682:Cation Transport Proteins / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005089:Exocytosis; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D050052:TRPC Cation Channels; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism*; D000077191:Wortmannin; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000730:Androstadienes; D015220:Calcium Channels; D027682:Cation Transport Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D009025:Morpholines; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D049452:Green Fluorescent Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D020830:rac1 GTP-Binding Protein; D000077191:Wortmannin