PMID:17404231

Citation	Anyatonwu, GI, Estrada, M, Tian, X, Somlo, S and Ehrlich, BE (2007) Regulation of ryanodine receptor-dependent calcium signaling by polycystin-2. Proc. Natl. Acad. Sci. U.S.A. 104:6454-9
Abstract	Mutations in polycystin-2 (PC2) cause autosomal dominant polycystic kidney disease. A function for PC2 in the heart has not been described. Here, we show that PC2 coimmunoprecipitates with the cardiac ryanodine receptor (RyR2) from mouse heart. Biochemical assays showed that the N terminus of PC2 binds the RyR2, whereas the C terminus only binds to RyR2 in its open state. Lipid bilayer electrophysiological experiments indicated that the C terminus of PC2 functionally inhibited RyR2 channel activity in the presence of calcium (Ca(2+)). Pkd2(-/-) cardiomyocytes had a higher frequency of spontaneous Ca(2+) oscillations, reduced Ca(2+) release from the sarcoplasmic reticulum stores, and reduced Ca(2+) content compared with Pkd2(+/+) cardiomyocytes. In the presence of caffeine, Pkd2(-/-) cardiomyocytes exhibited decreased peak fluorescence, a slower rate of rise, and a longer duration of Ca(2+) transients compared with Pkd2(+/+). These data suggest that PC2 is important for regulation of RyR2 function and that loss of this regulation of RyR2, as occurs when PC2 is mutated, results in altered Ca(2+) signaling in the heart.
Links	PubMed PMC1851053 Online version:10.1073/pnas.0610324104
Keywords	Animals; Caffeine/pharmacology; Calcium/metabolism; Electrophysiology; Immunoblotting; Immunoprecipitation; Mice; Mice, Knockout; Myocytes, Cardiac/metabolism; Ryanodine Receptor Calcium Release Channel/metabolism; TRPP Cation Channels/metabolism
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