Editors' ChoiceCalcium signaling

"TRPping" the Switch for Store-Operated Calcium Entry

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Science's STKE  11 Jan 2000:
Vol. 2000, Issue 14, pp. tw6
DOI: 10.1126/stke.2000.14.tw6

Agents that signal by increasing the intracellular concentration of free Ca2+ often cause both release of Ca2+ from intracellular stores and influx of Ca2+ through channels in the plasma membrane. In fact, the emptying of intracellular stores is somehow coupled to the activation of Ca2+ influx. Boulay et al. now help unravel two outstanding mysteries about this process—how store depletion is sensed and transmitted to the channel, and the nature of the membrane channels that actually mediate the Ca2+ influx. Their results show that TRP channels (named after Drosophila transient receptor potential mutants) directly interact with inositol 1,4,5-trisphosphate receptors (IP3R). Expression in cells of peptide fragments from the regions of the IP3 receptor that interact with TRP caused decreased Ca2+ entry in response to store depletion. The authors discuss, as does Putney in commentary on the paper, that the results implicate TRP channels as a component of the store depletion–activated Ca2+ entry system. One possibility is that the IP3R may undergo a comformational change in response to the decreased concentration of Ca2+ in the stores and physically transmit a signal to interacting TRP channels.

Boulay, G., Brown, D.M., Qin, N., Jiang, M., Dietrich, A., Zhu, M.X., Chen, Z., Birnbaumer, M., Mikoshiba, K., and Birnbaumer, L. (1999) Modulation of Ca2+ entry by polypeptides of the inositol 1,4,5-trisphosphate receptor (IP3R) that bind transient receptor potential (TRP): Evidence for roles of TRP and IP3R in store depletion-activated Ca2+ entry. Proc. Natl. Acad. Sci. U.S.A. 96:14955-14960. [Abstract] [Full Text]

Putney, J., (1999) TRP, inositol 1,4,5-trisphosphate receptors, and capacitative calcium entry. Proc. Natl. Acad. Sci. U.S.A. 96: 14669-14671. [Abstract] [Full Text]

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