TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel.
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.
Park
Jae-Yong
JY
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.
Hwang
Eun Mi
EM
Yarishkin
Oleg
O
Seo
Jin-Ho
JH
Kim
Eunju
E
Yoo
Jiyun
J
Yi
Gwan-Su
GS
Kim
Dong-Gyu
DG
Park
Nammi
N
Ha
Chang Man
CM
La
Jun-Ho
JH
Kang
Dawon
D
Han
Jaehee
J
Oh
Uhtaek
U
Hong
Seong-Geun
SG
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*
D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D002118:Calcium