title: Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents.
abstract: The human kidney is composed of roughly 1.2-million renal tubules that must maintain their tubular structure to function properly. In autosomal dominant polycystic kidney disease (ADPKD) cysts develop from renal tubules and enlarge independently, in a process that ultimately causes renal failure in 50% of affected individuals. Mutations in either PKD1 or PKD2 are associated with ADPKD but the function of these genes is unknown. PKD1 is thought to encode a membrane protein, polycystin-1, involved in cell-cell or cell-matrix interactions, whereas the PKD2 gene product, polycystin-2, is thought to be a channel protein. Here we show that polycystin-1 and -2 interact to produce new calcium-permeable non-selective cation currents. Neither polycystin-1 nor -2 alone is capable of producing currents. Moreover, disease-associated mutant forms of either polycystin protein that are incapable of heterodimerization do not result in new channel activity. We also show that polycystin-2 is localized in the cell in the absence of polycystin-1, but is translocated to the plasma membrane in its presence. Thus, polycystin-1 and -2 co-assemble at the plasma membrane to produce a new channel and to regulate renal tubular morphology and function.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hanaoka
authors.forename: F
authors.initials: F
authors.lastname: Qian
authors.forename: A
authors.initials: A
authors.lastname: Boletta
authors.forename: A K
authors.initials: AK
authors.lastname: Bhunia
authors.forename: K
authors.initials: K
authors.lastname: Piontek
authors.forename: L
authors.initials: L
authors.lastname: Tsiokas
authors.forename: V P
authors.initials: VP
authors.lastname: Sukhatme
authors.forename: W B
authors.initials: WB
authors.lastname: Guggino
authors.forename: G G
authors.initials: GG
authors.lastname: Germino
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002412:Cations / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004594:Electrophysiology; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050396:TRPP Cation Channels; D014162:Transfection
chemical_list: D002118:Calcium; D015220:Calcium Channels; D002412:Cations; D008565:Membrane Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D050396:TRPP Cation Channels