Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes

J Biol Chem. 2012 Jan 27;287(5):3530-40. doi: 10.1074/jbc.M111.283218. Epub 2011 Dec 8.

Abstract

Specific biological roles of the classical transient receptor potential channel 1 (TRPC1) are still largely elusive. To investigate the function of TRPC1 proteins in cell physiology, we studied heterologously expressed TRPC1 channels and found that recombinant TRPC1 subunits do not form functional homomeric channels. Instead, by electrophysiological analysis TRPC1 was shown to form functional heteromeric, receptor-operated channel complexes with TRPC3, -4, -5, -6, and -7 indicating that TRPC1 proteins can co-assemble with all members of the TRPC subfamily. In all TRPC1-containing heteromers, TRPC1 subunits significantly decreased calcium permeation. The exchange of select amino acids in the putative pore-forming region of TRPC1 further reduced calcium permeability, suggesting that TRPC1 subunits contribute to the channel pore. In immortalized immature gonadotropin-releasing hormone neurons endogenously expressing TRPC1, -2, -5, and -6, down-regulation of TRPC1 resulted in increased calcium permeability and elevated basal cytosolic calcium concentrations. We did not observe any involvement of TRPC1 in store-operated cation influx. Notably, TRPC1 suppressed the migration of gonadotropin-releasing hormone neurons without affecting cell proliferation. Conversely, in TRPC1 knockdown neurons, specific migratory properties like distance covered, locomotion speed, and directionality were increased. These findings suggest a novel regulatory mechanism relying on the expression of TRPC1 and the subsequent formation of heteromeric TRPC channel complexes with reduced calcium permeability, thereby fine-tuning neuronal migration.

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism*
  • Cell Movement / physiology*
  • Cricetinae
  • Cricetulus
  • Gene Expression Regulation / physiology
  • Gene Knockdown Techniques
  • Gonadotropin-Releasing Hormone / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • Neurons / cytology
  • Neurons / metabolism*
  • Permeability
  • Protein Structure, Quaternary
  • Rats
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPC6 Cation Channel

Substances

  • TRPC Cation Channels
  • TRPC3 cation channel
  • TRPC4 ion channel
  • TRPC5 protein, human
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • Trpc5 protein, mouse
  • Trpc5 protein, rat
  • transient receptor potential cation channel, subfamily C, member 1
  • Gonadotropin-Releasing Hormone
  • Calcium