Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC4 , TRPC5

Title: Conserved Gating Elements in TRPC4 and TRPC5 Channels.

Authors: Andreas Beck, Tilman Speicher, Christof Stoerger, Thomas Sell, Viviane Dettmer, Siti A Jusoh, Ammar Abdulmughni, Adolfo Cavalié, Stephan E Philipp, Michael X Zhu, Volkhard Helms, Ulrich Wissenbach, Veit Flockerzi

Journal, date & volume: J. Biol. Chem., 2013 Jul 5 , 288, 19471-83

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23677990

Abstract
TRPC4 and TRPC5 proteins share 65% amino acid sequence identity and form Ca(2+)-permeable nonselective cation channels. They are activated by stimulation of receptors coupled to the phosphoinositide signaling cascade. Replacing a conserved glycine residue within the cytosolic S4-S5 linker of both proteins by a serine residue forces the channels into an open conformation. Expression of the TRPC4G503S and TRPC5G504S mutants causes cell death, which could be prevented by buffering the Ca(2+) of the culture medium. Current-voltage relationships of the TRPC4G503S and TRPC5G504S mutant ion channels resemble that of fully activated TRPC4 and TRPC5 wild-type channels, respectively. Modeling the structure of the transmembrane domains and the pore region (S4-S6) of TRPC4 predicts a conserved serine residue within the C-terminal sequence of the predicted S6 helix as a potential interaction site. Introduction of a second mutation (S623A) into TRPC4G503S suppressed the constitutive activation and partially rescued its function. These results indicate that the S4-S5 linker is a critical constituent of TRPC4/C5 channel gating and that disturbance of its sequence allows channel opening independent of any sensor domain.