Editors' ChoiceTRP CHANNELS

Moving TRPs to the Membrane

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Science's STKE  07 Sep 2004:
Vol. 2004, Issue 249, pp. tw313
DOI: 10.1126/stke.2492004tw313

Singh et al. report that cation channels of the transient receptor potential (TRP) family are dynamically inserted into the plasma membrane in response to ligand stimulation of G protein-coupled receptors, as recently found following stimulation of receptor tyrosine kinases. The authors identified proteins involved in exocytosis, vesicle-associated membrane protein 2 (VAMP2) and α soluble N-ethylmaleimide-sensitive factor attachment protein (αSNAP), as interacting partners for the N-terminal domain of TRPC3 in a yeast two-hybrid screen. The interaction with proteins involved in exocytosis was confirmed with heterologously expressed proteins in transfected cells and endogenously expressed protein in rat brain. In surface biotinylation experiments, exposure of human embryonic kidney 293 (HEK293) cells expressing TRPC3 to the G protein-coupled receptor ligand carbachol resulted in increased abundance of TRPC3 at the cell surface, and this insertion was inhibited by cleavage of VAMP2 with tetanus toxin. The authors measured calcium influx with fluorescent indicators to verify that the channels were functional. Thus, regulated insertion of TRPC3 appears to be contribute to agonist-stimulated TRP activity and calcium signaling.

B. B. Singh, T. P. Lockwich, B. C. Bandyopadhyay, X. Liu, S. Bollimuntha, S. C. Brazer, C. Combs, S. Das, A. G. Leenders, Z.-H. Sheng, M. A. Knepper, S. V. Ambudkar, I. S. Ambudkar, VAMP2-dependent exocytosis regulates plasma membrane insertion of TRPC3 channels and contributes to agonist-stimulated Ca2+ influx. Mol. Cell 15, 635-646 (2004). [Online Journal]