STIM1 dimers undergo unimolecular coupling to activate Orai1 channels

Yandong Zhou, Xizhuo Wang, Xianming Wang, Natalia A. Loktionova, Xiangyu Cai, Robert M. Nwokonko, Erin Vrana, Youjun Wang, Brad S. Rothberg, Donald Gill

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored Ca 2+ is depleted and translocates into ER-plasma membrane junctions where it tethers and activates Orai1 Ca 2+ entry channels. The dimeric STIM1 protein contains a small STIM-Orai-Activating region (SOAR)-the minimal sequence sufficient to activate Orai1 channels. Since SOAR itself is a dimer, we constructed SOAR concatemer-dimers and introduced mutations at F394, which is critical for Orai1 coupling and activation. The F394H mutation in both SOAR monomers completely blocks dimer function, but F394H introduced in only one of the dimeric SOAR monomers has no effect on Orai1 binding or activation. This reveals an unexpected unimolecular coupling between STIM1 and Orai1 and argues against recent evidence suggesting dimeric interaction between STIM1 and two adjacent Orai1 channel subunits. The model predicts that STIM1 dimers may be involved in crosslinking between Orai1 channels with implications for the kinetics and localization of Orai1 channel opening.

Original languageEnglish (US)
Article number8395
JournalNature communications
Volume6
DOIs
StatePublished - Sep 24 2015

Fingerprint

Endoplasmic Reticulum
Dimers
endoplasmic reticulum
dimers
mutations
Mutation
Monomers
Chemical activation
monomers
activation
Cell membranes
Cell Membrane
Crosslinking
crosslinking
entry
Kinetics
Sensors
membranes
proteins
sensors

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zhou, Yandong ; Wang, Xizhuo ; Wang, Xianming ; Loktionova, Natalia A. ; Cai, Xiangyu ; Nwokonko, Robert M. ; Vrana, Erin ; Wang, Youjun ; Rothberg, Brad S. ; Gill, Donald. / STIM1 dimers undergo unimolecular coupling to activate Orai1 channels. In: Nature communications. 2015 ; Vol. 6.
@article{fef62c6126464c76ab1e7369c5dda0fa,
title = "STIM1 dimers undergo unimolecular coupling to activate Orai1 channels",
abstract = "The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored Ca 2+ is depleted and translocates into ER-plasma membrane junctions where it tethers and activates Orai1 Ca 2+ entry channels. The dimeric STIM1 protein contains a small STIM-Orai-Activating region (SOAR)-the minimal sequence sufficient to activate Orai1 channels. Since SOAR itself is a dimer, we constructed SOAR concatemer-dimers and introduced mutations at F394, which is critical for Orai1 coupling and activation. The F394H mutation in both SOAR monomers completely blocks dimer function, but F394H introduced in only one of the dimeric SOAR monomers has no effect on Orai1 binding or activation. This reveals an unexpected unimolecular coupling between STIM1 and Orai1 and argues against recent evidence suggesting dimeric interaction between STIM1 and two adjacent Orai1 channel subunits. The model predicts that STIM1 dimers may be involved in crosslinking between Orai1 channels with implications for the kinetics and localization of Orai1 channel opening.",
author = "Yandong Zhou and Xizhuo Wang and Xianming Wang and Loktionova, {Natalia A.} and Xiangyu Cai and Nwokonko, {Robert M.} and Erin Vrana and Youjun Wang and Rothberg, {Brad S.} and Donald Gill",
year = "2015",
month = "9",
day = "24",
doi = "10.1038/ncomms9395",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

Zhou, Y, Wang, X, Wang, X, Loktionova, NA, Cai, X, Nwokonko, RM, Vrana, E, Wang, Y, Rothberg, BS & Gill, D 2015, 'STIM1 dimers undergo unimolecular coupling to activate Orai1 channels', Nature communications, vol. 6, 8395. https://doi.org/10.1038/ncomms9395

STIM1 dimers undergo unimolecular coupling to activate Orai1 channels. / Zhou, Yandong; Wang, Xizhuo; Wang, Xianming; Loktionova, Natalia A.; Cai, Xiangyu; Nwokonko, Robert M.; Vrana, Erin; Wang, Youjun; Rothberg, Brad S.; Gill, Donald.

In: Nature communications, Vol. 6, 8395, 24.09.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - STIM1 dimers undergo unimolecular coupling to activate Orai1 channels

AU - Zhou, Yandong

AU - Wang, Xizhuo

AU - Wang, Xianming

AU - Loktionova, Natalia A.

AU - Cai, Xiangyu

AU - Nwokonko, Robert M.

AU - Vrana, Erin

AU - Wang, Youjun

AU - Rothberg, Brad S.

AU - Gill, Donald

PY - 2015/9/24

Y1 - 2015/9/24

N2 - The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored Ca 2+ is depleted and translocates into ER-plasma membrane junctions where it tethers and activates Orai1 Ca 2+ entry channels. The dimeric STIM1 protein contains a small STIM-Orai-Activating region (SOAR)-the minimal sequence sufficient to activate Orai1 channels. Since SOAR itself is a dimer, we constructed SOAR concatemer-dimers and introduced mutations at F394, which is critical for Orai1 coupling and activation. The F394H mutation in both SOAR monomers completely blocks dimer function, but F394H introduced in only one of the dimeric SOAR monomers has no effect on Orai1 binding or activation. This reveals an unexpected unimolecular coupling between STIM1 and Orai1 and argues against recent evidence suggesting dimeric interaction between STIM1 and two adjacent Orai1 channel subunits. The model predicts that STIM1 dimers may be involved in crosslinking between Orai1 channels with implications for the kinetics and localization of Orai1 channel opening.

AB - The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored Ca 2+ is depleted and translocates into ER-plasma membrane junctions where it tethers and activates Orai1 Ca 2+ entry channels. The dimeric STIM1 protein contains a small STIM-Orai-Activating region (SOAR)-the minimal sequence sufficient to activate Orai1 channels. Since SOAR itself is a dimer, we constructed SOAR concatemer-dimers and introduced mutations at F394, which is critical for Orai1 coupling and activation. The F394H mutation in both SOAR monomers completely blocks dimer function, but F394H introduced in only one of the dimeric SOAR monomers has no effect on Orai1 binding or activation. This reveals an unexpected unimolecular coupling between STIM1 and Orai1 and argues against recent evidence suggesting dimeric interaction between STIM1 and two adjacent Orai1 channel subunits. The model predicts that STIM1 dimers may be involved in crosslinking between Orai1 channels with implications for the kinetics and localization of Orai1 channel opening.

UR - http://www.scopus.com/inward/record.url?scp=84942134772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942134772&partnerID=8YFLogxK

U2 - 10.1038/ncomms9395

DO - 10.1038/ncomms9395

M3 - Article

C2 - 26399906

AN - SCOPUS:84942134772

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 8395

ER -