Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1.
Science
; 377(6612): 1290-1298, 2022 09 16.
Article
em En
| MEDLINE
| ID: mdl-36007018
ABSTRACT
Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients, including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation of the master growth regulator, the protein kinase mechanistic target of rapamycin complex 1 (mTORC1). Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation. At high cholesterol concentrations, LYCHOS bound to the GATOR1 complex, a guanosine triphosphatase (GTPase)-activating protein for the Rag GTPases, through a conserved cytoplasm-facing loop. By sequestering GATOR1, LYCHOS promotes cholesterol- and Rag-dependent recruitment of mTORC1 to lysosomes. Thus, LYCHOS functions in a lysosomal pathway for cholesterol sensing and couples cholesterol concentrations to mTORC1-dependent anabolic signaling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colesterol
/
Receptores Acoplados a Proteínas G
/
Alvo Mecanístico do Complexo 1 de Rapamicina
/
Lisossomos
Limite:
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos