Inhibitor of Myogenic Family, a Novel Suppressor of Store-operated Currents through an Interaction with TRPC1

Rong Ma, Dana Rundle, Jeanie Jacks, Marci Koch, Tamyra Downs, Leonidas Tsiokas

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Depletion of intracellular Ca2+ stores leads to the activation of Ca2+ inflow through store-operated Ca2+ channels. Although the identity of these channels is unknown, there is considerable evidence that the transient receptor potential channel 1 (TRPC1) participates in the formation of these channels. We show that TRPC1 physically interacts with the a-isoform of the inhibitor of the myogenic family (I-mfa), a known inhibitor of basic helix-loop-helix transcription factors, in vitro and in vivo. The interaction is mediated by the C-terminal cytoplasmic tail of TRPC1 and the C-terminal cysteine-rich domain of I-mfa. Using the whole cell configuration of the patch clamp technique, we show that ectopic expression of I-mfa in CHO-K1 cells reduces native store-activated Ca2+ currents, whereas knock-down of endogenous I-mfa in A431 cells by RNA interference enhances these currents. Pipette perfusion of purified recombinant I-mfa rescues the effect of I-mfa knock-down on store-operated conductance. Finally, cell dialysis with a monoclonal antibody specific to TRPC1 results in the suppression of store-activated conductance in cells lacking I-mfa, but not in I-mfa expressing cells. We propose that I-mfa functions as a molecular switch to suppress the store dependence of TRPC1.

Original languageEnglish
Pages (from-to)52763-52772
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number52
DOIs
StatePublished - 26 Dec 2003

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