Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis elegans.
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.
Koulen
Peter
P
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 76107-2699, USA. pkoulen@hsc.unt.edu
Duncan
R Scott
RS
Liu
Jiyuan
J
Cohen
Nancy E
NE
Yannazzo
Jo-Ann S
JA
McClung
Nathalie
N
Lockhart
Courtney L
CL
Branden
Michael
M
Buechner
Matthew
M
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
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