@article{oai:kanazawa-u.repo.nii.ac.jp:00014458,
 author = {Miyagi, Kyoko and Kiyonaka, Shigeki and Yamada, Kazunori and Miki, Takafumi and Mori, Emiko and Kato, Kenta and Numata, Tomohiro and Sawaguchi, Yuichi and Numaga, Takuro and Kimura, Toru and Kanai, Yoshikatsu and Kawano, Mitsuhiro and Wakamori, Minoru and Nomura, Hideki and Koni, Ichiro and Yamagishi, Masakazu and Mori, Yasuo},
 issue = {49},
 journal = {Journal of Biological Chemistry},
 month = {Dec},
 note = {Mutations in PKD2 gene result in autosomal dominant polycystic kidney disease (ADPKD). PKD2 encodes polycystin-2 (TRPP2), which is a homologue of transient receptor potential (TRP) cation channel proteins. Here we identify a novel PKD2 mutation that generates a C-terminal tail-truncated TRPP2 mutant 697fsX with a frameshift resulting in an aberrant 17-amino acid addition after glutamic acid residue 697 from a family showing mild ADPKD symptoms. When recombinantly expressed in HEK293 cells, wild-type (WT) TRPP2 localized at the endoplasmic reticulum (ER) membrane significantly enhanced Ca2+ release from the ER upon muscarinic acetylcholine receptor (mAChR) stimulation. In contrast, 697fsX, which showed a predominant plasma membrane localization characteristic of TRPP2 mutants with C terminus deletion, prominently increased mAChR-activated influx in cells expressing TRPC3 or TRPC7. Coimmunoprecipitation, pulldown assay, and cross-linking experiments revealed a physical association between 697fsX and TRPC3 or TRPC7. 697fsX but not WT TRPP2 elicited a depolarizing shift of reversal potentials and an enhancement of single-channel conductance indicative of altered ion-permeating pore properties of mAChR-activated currents. Importantly, in kidney epithelial LLC-PK1 cells the recombinant 679fsX construct was codistributed with native TRPC3 proteins at the apical membrane area, but the WT construct was distributed in the basolateral membrane and adjacent intracellular areas. Our results suggest that heteromeric cation channels comprised of the TRPP2 mutant and the TRPC3 or TRPC7 protein induce enhanced receptor-activated Ca2+ influx that may lead to dysregulated cell growth in ADPKD. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc., Publisher's version/PDF may be used after 12 months embargo},
 pages = {34400--34412},
 title = {A pathogenic C terminus-truncated polycystin-2 mutant enhances receptor-activated Ca2+ entry via association with TRPC3 and TRPC7.},
 volume = {284},
 year = {2009}
}