Evolutionary conservation of Drosophila polycystin-2 as a calcium-activated cation channel.
Mutations in the PKD2 gene cause autosomal dominant polycystic kidney disease (ADPKD) in humans. The protein encoded by PKD2 has similarity to voltage-sensitive cation channels and TRP channels and was named polycystin-2 (PC2). In agreement with this structural information, expression of PC2 in Xenopus oocytes or reconstitution of human PC2 in planar lipid bilayers produced Ca(2+)-activated cation channels. Although these studies provided a basic description of the biophysical, regulatory, and pharmacologic properties of the PC2-induced channels, it is still unknown how defective PC2 activity leads to cyst formation and expansion in ADPKD patients. To establish a genetic model for studying PC2 function and regulation, the authors identified and cloned a Drosophila PC2 (DmPC2). It is here shown that expression of DmPKD2 in Drosophila S2 cells produced a novel channel. On the basis of the similarity of this channel's properties to mammalian PKD2-induced channels, this Drosophila channel is expected to provide a convenient genetic model for dissecting the mechanisms underlying ADPKD.
Venglarik
Charles J
CJ
Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. cjv@uab.edu
Gao
Zhiqian
Z
Lu
Xiangyi
X
D000595:Amino Acid Sequence; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism; D050396:TRPP Cation Channels; D014981:Xenopus
D001464:Barium; D002118:Calcium; D015220:Calcium Channels; D008565:Membrane Proteins; D012964:Sodium; D050396:TRPP Cation Channels