The interactions of the C-terminal region of the TRPC6 channel with calmodulin

Neurochem Int. 2010 Jan;56(2):363-6. doi: 10.1016/j.neuint.2009.11.009. Epub 2009 Nov 20.

Abstract

The transient receptor potential channel TRPC6 is a non-selective cation channel which modulates the calcium level in eukaryotic cells (including sensory receptor cells) in response to external signals. Calmodulin (CaM) is a ubiquitously expressed Ca(2+) binding protein that is an important mediator of Ca(2+)-dependent regulation of the TRPC6 channel. One CaM binding site was identified within the C-tail of TRPC6. The aim of this study is to map in detail the CaM and inositol (1,4,5)-triphosphate receptor binding (CIRB) domain in the C-terminal region of mouse TRPC6 that is capable of interacting with CaM using in vitro binding assays. Besides the set of positively charged amino acid residues Arg852, Lys856, Arg864, Lys859/Arg860, a hydrophobic Ile857, at the position 1 in 1-5-10 motif, was located and the effect of replacing it with a neutral residue was tested using fluorescence anisotropy measurement. Participation of Ile857 could indicate a strong role of this conserved CaM binding motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calmodulin / metabolism*
  • Cloning, Molecular
  • Electrophoretic Mobility Shift Assay
  • Fluorescence Polarization
  • Mice
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • TRPC Cation Channels / chemistry
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*

Substances

  • Calmodulin
  • TRPC Cation Channels
  • Trpc6 protein, mouse