Referenced in: none

Automatically associated channels: Slo1

Title: The short N-terminal domains of STIM1 and STIM2 control the activation kinetics of Orai1 channels.

Authors: Yandong Zhou, Salvatore Mancarella, Youjun Wang, Chanyu Yue, Michael Ritchie, Donald L Gill, Jonathan Soboloff

Journal, date & volume: J. Biol. Chem., 2009 Jul 17 , 284, 19164-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19487696

Abstract
STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca(2+) sensors, coupling directly to activate plasma membrane Orai Ca(2+) entry channels. Despite extensive sequence homology, the STIM proteins are functionally distinct. We reveal that the short variable N-terminal random coil sequences of STIM1 and STIM2 confer profoundly different activation properties. Using Orai1-expressing HEK293 cells, chimeric replacement of the 43-amino-acid STIM1 N terminus with that of STIM2 attenuates Orai1-mediated Ca(2+) entry and drastically slows store-induced Orai1 channel activation. Conversely, the 55-amino-acid STIM2 terminus substituted within STIM1 strikingly enhances both Orai1-mediated Ca(2+) entry and constitutive coupling to activate Orai1 channels. Hence, STIM N termini are powerful coupling modifiers, functioning in STIM2 to "brake" the otherwise constitutive activation of Orai1 channels afforded by its high sensitivity to luminal Ca(2+).