Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits.
Although several protein-protein interactions have been reported between transient receptor potential (TRP) channels, they are all known to occur exclusively between members of the same group. The only intergroup interaction described so far is that of TRPP2 and TRPC1; however, the significance of this interaction is unknown. Here, we show that TRPP2 and TRPC1 assemble to form a channel with a unique constellation of new and TRPP2/TRPC1-specific properties. TRPP2/TRPC1 is activated in response to G-protein-coupled receptor activation and shows a pattern of single-channel conductance, amiloride sensitivity and ion permeability distinct from that of TRPP2 or TRPC1 alone. Native TRPP2/TRPC1 activity is shown in kidney cells by complementary gain-of-function and loss-of-function experiments, and its existence under physiological conditions is supported by colocalization at the primary cilium and by co-immunoprecipitation from kidney membranes. Identification of the heteromultimeric TRPP2/TRPC1 channel has implications in mechanosensation and cilium-based Ca(2+) signalling.
Bai
Chang-Xi
CX
University of Oklahoma Health Sciences Center, 975 NE 10th Street, Oklahoma City, Oklahoma 73104, USA.
Giamarchi
Aurélie
A
Rodat-Despoix
Lise
L
Padilla
Françoise
F
Downs
Tamyra
T
Tsiokas
Leonidas
L
Delmas
Patrick
P
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism; D007473:Ion Channels / Q000096:biosynthesis*; D007668:Kidney / Q000166:cytology; D018374:LLC-PK1 Cells; D028581:Lanthanoid Series Elements / Q000494:pharmacology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013552:Swine; D050396:TRPP Cation Channels / Q000737:chemistry* / Q000378:metabolism
D000584:Amiloride; D007473:Ion Channels; D028581:Lanthanoid Series Elements; D018721:Muscarinic Agonists; D010095:Oxotremorine; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled; D026941:Sodium Channel Blockers; D050396:TRPP Cation Channels; C042743:oxotremorine M