Biochem Biophys Res Commun. 2008 Apr 11;368(3):677-83. Epub 2008 Feb 8.

TRPM4b channel suppresses store-operated Ca2+ entry by a novel protein-protein interaction with the TRPC3 channel.External

Park, J. Y., Hwang, E. M., Yarishkin, O., Seo, J. H., Kim, E., Yoo, J., Yi, G. S., Kim, D. G., Park, N., Ha, C. M., La, J. H., Kang, D., Han, J., Oh, U., Hong, S. G.,
["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."]
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.
PMID: 18262493External
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Screening Toggle
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC3 Link TRPM4 Yeast two-hybrid Not used as a bait Human Brain cDNA library 18262493
TRPM4 Link TRPC3 Yeast two-hybrid Human Full-length Human Brain cDNA library 18262493
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
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Validation: In vitro validation Toggle
  Assay with recombinant proteins Reference
TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Expression system Species Region Expression system
TRPC3 Link TRPM4 Yeast two-hybrid Human Full-length Yeast Human Full-length Yeast 18262493
TRPM4 Link TRPC3 Yeast two-hybrid Human Full-length Yeast Human Full-length Yeast 18262493
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Validation: In vivo validation Toggle
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC3 Link TRPM4 Co-immunoprecipitation HEK293T Human Full-length Human Full-length 18262493
TRPC3 Link TRPM4 Co-immunofluorescence staining HEK293T Human Full-length Human Full-length 18262493
TRPM4 Link TRPC3 Co-immunoprecipitation HEK293T Human Full-length Human Full-length 18262493
TRPM4 Link TRPC3 Co-immunofluorescence staining HEK293T Human Full-length Human Full-length 18262493
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Characterization Toggle
  Binding region mapping Stoichiometry Affinity (Kd) Reference
TRP channel Interactor
TRP channel Interactor Method Species Region Species Region
TRPC3 Link TRPM4 Co-immunoprecipitation Human Not determined Human 858-1188 18262493
TRPM4 Link TRPC3 Co-immunoprecipitation Human 858-1188 Human Not determined 18262493
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Arrow2 Screening Arrow2 Validation: In vitro validation Arrow2 Validation: In vivo validation Arrow2 Characterization Arrow2 Functional consequence Arrow2 top
Functional consequence Toggle
TRP channel Interactor Method Post-translational modification Subcellular trafficking Activity Reference
TRPC3 Link TRPM4 Patch clamp Inhibition 18262493
(Link: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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