Article abstract
Nature Cell Biology 6, 709 - 720 (2004)
Published online: 18 July 2004 | doi:10.1038/ncb1150
Rapid vesicular translocation and insertion of TRP channels
Vassilios J. Bezzerides1,2, I. Scott Ramsey1, Suhas Kotecha1, Anna Greka1,3 & David E. Clapham1
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 Ca2+-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
). The increase in TRPC5 availability affects neurite extension rates in cultured hippocampal neurons, and may be a general mechanism for initiating Ca2+ influx and cell morphological changes in response to stimuli.
- Howard Hughes Medical Institute, Cardiovascular Department, Children's Hospital and Harvard Medical School, Enders 1309 320 Longwood Avenue, Boston, MA 02115, USA.
- Program in Biophysics, Harvard Graduate School of Arts and Sciences, Cambridge, MA 02318, USA.
- Harvard Medical School and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02115, USA.
Correspondence to: David E. Clapham1 e-mail: dclapham@enders.tch.harvard.edu
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