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Sci. STKE, 12 June 2001
Vol. 2001, Issue 86, p. tw9
[DOI: 10.1126/stke.2001.86.tw9]


Channels Inhibiting the Chaperone

Many voltage-gated calcium channels have a pore-forming α subunit and a regulatory β subunit. Using yeast two-hybrid screens and assays, glutathione S-transferase fusion protein pull-down experiments, and coimmunoprecipitation experiments, Béguin et al. found that the β subunits interact with a small guanosine triphosphatase (GTPase) of the Ras family, kir/Gem. Kir/Gem has a Ca2+-calmodulin-binding domain, and the interaction with the β subunits, which occurs with the GTP-bound form of the GTPase, is inhibited in vitro by the presence of Ca2+ and calmodulin. Functionally, the coexpression of the kir/Gem protein with the β subunit and the α subunit inhibited Ca2+ currents in Xenopus oocytes or transfected mammalian cells. Inhibition required the presence of the β subunit and resulted from the decreased delivery of the channel to the cell surface. This decreased surface delivery is presumably due to the ability of kir/Gem to block the interaction of the α and the β subunits, which is required for the chaperone function of the β subunit. Transfection of kir/Gem into the calcium-dependent hormone secreting cell lines (PC12 and MIN6) inhibited Ca2+ channel currents and hormone secretion, showing a potential physiological role for kir/Gem.

P. Béguin, K. Nagashima, T. Gonoi, T. Shibasaki, K. Takahashi, Y. Kashima, N. Ozaki, K. Geering, T. Iwanga, S. Seino, Regulation of Ca2+ expression at the cell surface by the small G-protein kir/Gem. Nature 411, 701-706 (2001). [Online Journal]

Citation: Inhibiting the Chaperone. Sci. STKE 2001, tw9 (2001).

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