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

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• 作者：Jae-Yong Park ; Eun Mi Hwang ; Oleg Yarishkin ; Jin-Ho Seo ; Eunju Kim ; Jiyun Yoo ; Gwan-Su Yi ; Dong-Gyu Kim ; Nammi Park ; Chang Man Ha ; Jun-ho La ; Dawon Kang ; Jaehee Han ; Uhtaek Oh ; Seong-Geun Hong
• 关键词：Store-operated Ca²⁺ entry ; TRPC3 ; TRPM4b ; Yeast two-hybrid
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：11 April 2008
• 年：2008
• 卷：368
• 期：3
• 页码：677-683
• 全文大小：1517 K

文摘

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 Ca²⁺ 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 Ca²⁺ entry through the TRPC3 channel.