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

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

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca2+ sensors, coupling directly to activate plasma membrane Orai Ca2+ 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 Ca2+ entry and drastically slows store-induced Orai1 channel activation. Conversely, the 55-amino-acid STIM2 terminus substituted within STIM1 strikingly enhances both Orai1-mediated Ca2+ 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 Ca2+.

Original languageEnglish (US)
Pages (from-to)19164-19168
Number of pages5
JournalJournal of Biological Chemistry
Volume284
Issue number29
DOIs
StatePublished - Jul 17 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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