title: TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel.
abstract: We identified human TRPC3 protein by yeast two-hybrid screening of a human brain cDNA library with human TRPM4b as a bait. Immunoprecipitation and confocal microscopic analyses confirmed the protein-protein interaction between TRPM4b and TRPC3, and these two TRPs were found to be highly colocalized at the plasma membrane of HEK293T cells. Overexpression of TRPM4b suppressed TRPC3-mediated whole cell currents by more than 90% compared to those in TRPC3-expressed HEK293T cells. Furthermore, HEK293T cells stably overexpressing red fluorescent protein (RFP)-TRPM4b exhibited an almost complete abolition of UTP-induced store-operated Ca(2+) entry, which is known to take place via endogenous TRPC channels in HEK293T cells. This study is believed to provide the first clear evidence that TRPM4b interacts physically with TRPC3, a member of a different TRP subfamily, and regulates negatively the channel activity, in turn suppressing store-operated Ca(2+) entry through the TRPC3 channel.
authors.affiliation: Department of Physiology, Institute of Health Science, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Oleg
authors.initials: O
authors.lastname: Yarishkin
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Seo
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
authors.forename: Gwan-Su
authors.initials: GS
authors.lastname: Yi
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Kim
authors.forename: Nammi
authors.initials: N
authors.lastname: Park
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: La
authors.forename: Dawon
authors.initials: D
authors.lastname: Kang
authors.forename: Jaehee
authors.initials: J
authors.lastname: Han
authors.forename: Uhtaek
authors.initials: U
authors.lastname: Oh
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D050052:TRPC Cation Channels / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D002118:Calcium