More Pairs of SOCS

Abstract

Capacitative calcium entry (CCE) refers to Ca2+ influx across the plasma membrane (PM) that occurs in response to calcium release from intracellular stores. One proposed regulatory mechanism in vertebrate cells involves the physical and functional coupling of IP3-activated calcium release channels (IP3Rs) present in store membranes with store-operated channels (SOCs). When activated, IP3Rs are thought to undergo a conformational change that couples to the opening of SOCs in the PM. Two papers suggest that there may be additional channels and mechanisms that can contribute to CCE: Kiselyov et al. have found gating of SOCs by ryanodine receptors (RyRs) and Locke et al. have identified a CCE mechanism in yeast that involves a channel with homology to voltage-gated Ca2+ channels. Kiselyov et al. demonstrate that, like IP3Rs, RyRs appeared to gate the store-operated calcium channels hTrp3 and Icrac in whole cells and in membrane patches when RyRs were stimulated with caffeine. hTrp3 channels coimmunoprecipitated with either IP3Rs or RyRs but not both, suggesting that although both receptors are present in store membranes, their interaction with SOCs is mutually exclusive. The authors also found that cell membrane patches contained SOCs coupled to either IP3Rs or RyRs, but not to both simultaneously, and suggest that the pairs are present in separate membrane microdomains. Yeasts are also capable of using calcium as a second messenger and have increased concentrations of calcium in the organelles of the secretory pathway. Using a genetic screen designed to detect mutants defective in CCE, Locke et al. identified two proteins required for CCE in yeast: Cch1p, a PM SOC that has structural homology to voltage-gated Ca2+ channels and a PM glycoprotein, Mid1p. Disruption of the genes for CCH1 or MID1 abolished high-affinity Ca2+ influx associated with conditions that stimulated CCE. The yeast model of CCE involves the Golgi Ca2+ -ATPase, which sequesters calcium in the secretory organelles, and Cch1p and Mid1p, which are localized to the PM and stimulate Ca2+ influx required for store replenishment.Kiselyov, K.I., Shin, D.M., Wang, Y., Pessah, I.N., Allen, P.D., and Muallem, S. (2000) Gating of store-operated channels by conformational coupling to ryanodine receptors. Mol. Cell 6: 421-431. [Online Journal]Locke, E.G., Bonilla, M., Liang, L., Takita, Y., and Cunningham, K.W. (2000) A homolog of voltage-gated Ca2+ channels stimulated by depletion of secretory Ca2+ in yeast. Mol. Cell. Biol. 20: 6686-6694. [Abstract] [Full Text]