G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling.
Cell
; 184(3): 655-674.e27, 2021 02 04.
Article
em En
| MEDLINE
| ID: mdl-33497611
ABSTRACT
Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esclerose Tuberosa
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Transdução de Sinais
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Proteínas de Ligação a RNA
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DNA Helicases
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RNA Helicases
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas com Motivo de Reconhecimento de RNA
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Proteínas de Ligação a Poli-ADP-Ribose
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Lisossomos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article