Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Jun:80:192-193.
doi: 10.1016/j.ceca.2019.03.003. Epub 2019 Mar 7.

STIM1 holds a STING in its (N-terminal) tail

Aran Son  1 , Adriana Almeida de Jesus  2 , Daniella M Schwartz  3
Affiliations
Comment

STIM1 holds a STING in its (N-terminal) tail

Aran Son et al. Cell Calcium. 2019 Jun.

Abstract

The Ca2+ sensor STIM1 is essential for adaptive immune responses, yet patients with hypomorphic STIM1 mutations develop both immunodeficiency and autoimmunity, implying that STIM1 also restrains immune responses. This study by Srikanth et al demonstrates that STIM1 tethers STING, a major inducer of the interferon (IFN) response, to the endoplasmic reticulum (ER) to prevent constitutive STING activation.

PubMed Disclaimer

Figures

None
In the resting state, STIM1 is bound to STING within the endoplasmic reticulum (ER). This interaction retains STING in the ER, preventing activation. In the absence of STIM1, STING constitutively trafficks to the ER-Golgi compartment (ERGIC), recruits TANK-binding kinase (TBK), and activates interferon regulatory factor 3 (IRF3). IRF3 dimerizes, translocates to the nucleus, and acts as an activating transcription factor for type I interferon and other proinflammatory genes.
See this image and copyright information in PMC

Comment on

References

    1. Srikanth S, et al., The Ca(2+) sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum. Nat Immunol, 2019. 20(2): p. 152–162. - PMC - PubMed
    1. Son A, et al., Orai1 and STIM1 in ER/PM junctions: roles in pancreatic cell function and dysfunction. Am J Physiol Cell Physiol, 2016. 310(6): p. C414–22. - PMC - PubMed
    1. Vaeth M and Feske S, Ion channelopathies of the immune system. Curr Opin Immunol, 2018. 52: p. 39–50. - PMC - PubMed
    1. Liu Y, et al., Activated STING in a vascular and pulmonary syndrome. N Engl J Med, 2014. 371(6): p. 507–518. - PMC - PubMed
    1. Liu YP, et al., Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3. J Immunol, 2012. 189(9): p. 4630–9. - PMC - PubMed