TRPC3-interacting triadic proteins in skeletal muscle

Jin Seok Woo, Do Han Kim, Paul D. Allen, Eun Hui Lee

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

The expression of TRPC3 (canonical-type transient receptor potential cation channel type 3) is tightly regulated during skeletal muscle cell differentiation, and a functional interaction between TRPC3 and RyR1 [(ryanodine receptor type 1 ), an SR (sarcoplasmic reticulum) Ca2+-release channel] regulates the gain of SR Ca2+ release during EC (excitation-contraction) coupling. However, it has not been possible to demonstrate direct protein-protein interactions between TRPC3 and RyR1. To identify possible candidate(s) for a linker protein(s) between TRPC3 and RyR1 in skeletal muscle, in the present study we performed MALDITOF (matrix-assisted laser-desorption ionization-time-of-flight) MS analysis of a cross-linked triadic protein complex from rabbit skeletal triad vesicles and co-immunoprecipitation assays using primary mouse skeletal myotubes. From these studies, we found that six triadic proteins, that are known to regulate RyR1 function and/or EC coupling [TRPC1, JP2 (junctophilin 2), homer, mitsugumin 29, calreticulin and calmodulin], interacted directly with TRPC3 in a Ca 2+-independent manner. However we again found no direct interaction between TRPC3 and RyR1. TRPC1 was identified as a potential physical link between TRPC3 and RyR1, as it interacted with both TRPC3 and RyR1, and JPs showed subtype-specific interactions with both RyR1 and TRPC3 (JP1-RyR1 and JP2-TRPC3). These results support the hypothesis that TRPC3 and RyR1 are functionally engaged via linker proteins in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)399-405
Number of pages7
JournalBiochemical Journal
Volume411
Issue number2
DOIs
StatePublished - Apr 15 2008
Externally publishedYes

Keywords

  • Canonical-type transient receptor potential cation channel 1 (TRPC1)
  • Junctophilin
  • Ryanodine receptor (RyR)
  • TRPC3

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)

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