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Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans
Authors:Koulen Peter  Duncan R Scott  Liu Jiyuan  Cohen Nancy E  Yannazzo Jo-Ann S  McClung Nathalie  Lockhart Courtney L  Branden Michael  Buechner Matthew
Institution:Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. pkoulen@hsc.unt.edu
Abstract:Polycystin-2, a member of the TRP family of calcium channels, is encoded by the human PKD2 gene. Mutations in that gene can lead to swelling of nephrons into the fluid-filled cysts of polycystic kidney disease. In addition to expression in tubular epithelial cells, human polycystin-2 is found in muscle and neuronal cells, but its cell biological function has been unclear. A homologue in Caenorhabditis elegans is necessary for male mating behavior. We compared the behavior, calcium signaling mechanisms, and electrophysiology of wild-type and pkd-2 knockout C. elegans. In addition to characterizing PKD-2-mediated aggregation and mating behaviors, we found that polycystin-2 is an intracellular Ca(2+) release channel that is required for the normal pattern of Ca(2+) responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release from intracellular stores. Activity of polycystin-2 creates brief cytosolic Ca(2+) transients with increased amplitude and decreased duration. Polycystin-2, along with the IP(3) and ryanodine receptors, acts as a major calcium-release channel in the endoplasmic reticulum in cells where rapid calcium signaling is required, and polycystin-2 activity is essential in those excitable cells for rapid responses to stimuli.
Keywords:Polycystic kidney disease  Calcium  Endoplasmic reticulum  Ryanodine receptor  IP3 receptor  PKD  TRP channel
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