The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA.
EMBO Rep
; 23(1): e53166, 2022 01 05.
Article
em En
| MEDLINE
| ID: mdl-34779554
ABSTRACT
Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA Helicases
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RNA Helicases
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Proteínas com Motivo de Reconhecimento de RNA
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Proteínas de Ligação a Poli-ADP-Ribose
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Nucleotidiltransferases
Idioma:
En
Revista:
EMBO Rep
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China