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

68 Citations (Scopus)

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

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Chemical activation
Amino Acids
Kinetics
HEK293 Cells
Sequence Homology
Endoplasmic Reticulum
Cell Membrane
Cell membranes
Brakes
Proteins
Sensors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The short N-terminal domains of STIM1 and STIM2 control the activation kinetics of Orai1 channels. / Zhou, Yandong; Mancarella, Salvatore; Wang, Youjun; Yue, Chanyu; Ritchie, Michael; Gill, Donald L.; Soboloff, Jonathan.

In: Journal of Biological Chemistry, Vol. 284, No. 29, 17.07.2009, p. 19164-19168.

Research output: Contribution to journalArticle

Zhou, Yandong ; Mancarella, Salvatore ; Wang, Youjun ; Yue, Chanyu ; Ritchie, Michael ; Gill, Donald L. ; Soboloff, Jonathan. / The short N-terminal domains of STIM1 and STIM2 control the activation kinetics of Orai1 channels. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 29. pp. 19164-19168.
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AU - Zhou, Yandong

AU - Mancarella, Salvatore

AU - Wang, Youjun

AU - Yue, Chanyu

AU - Ritchie, Michael

AU - Gill, Donald L.

AU - Soboloff, Jonathan

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AB - 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+.

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