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

37 Citations (Scopus)

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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Transient Receptor Potential Channels
Basic Helix-Loop-Helix Transcription Factors
Dialysis
CHO Cells
Clamping devices
Patch-Clamp Techniques
RNA Interference
Cysteine
Protein Isoforms
Perfusion
Chemical activation
Monoclonal Antibodies
Switches
RNA

Cite this

Ma, Rong ; Rundle, Dana ; Jacks, Jeanie ; Koch, Marci ; Downs, Tamyra ; Tsiokas, Leonidas. / Inhibitor of Myogenic Family, a Novel Suppressor of Store-operated Currents through an Interaction with TRPC1. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 52. pp. 52763-52772.
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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.",
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Inhibitor of Myogenic Family, a Novel Suppressor of Store-operated Currents through an Interaction with TRPC1. / Ma, Rong; Rundle, Dana; Jacks, Jeanie; Koch, Marci; Downs, Tamyra; Tsiokas, Leonidas.

In: Journal of Biological Chemistry, Vol. 278, No. 52, 26.12.2003, p. 52763-52772.

Research output: Contribution to journalArticle

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AU - Rundle, Dana

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