title: Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans.
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.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. pkoulen@hsc.unt.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
authors.forename: R Scott
authors.initials: RS
authors.lastname: Duncan
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Liu
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Cohen
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Yannazzo
authors.forename: Nathalie
authors.initials: N
authors.lastname: McClung
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Lockhart
authors.forename: Michael
authors.initials: M
authors.lastname: Branden
authors.forename: Matthew
authors.initials: M
authors.lastname: Buechner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000502:physiology; D050396:TRPP Cation Channels
chemical_list: D002118:Calcium; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008565:Membrane Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D050396:TRPP Cation Channels; C506926:ITPR1 protein, human