TMEM55B contributes to lysosomal homeostasis and amino acid-induced mTORC1 activation.
Genes Cells
; 23(6): 418-434, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29644770
Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) responds to growth factors and nutrient availability. Amino acids induce the recruitment of mTORC1 to the lysosomal membrane and its consequent activation, but the molecular mechanism of such activation has remained unclear. We have now examined the role of TMEM55B, a lysosomal protein of unknown molecular function, in this process on the basis of the results of proteomics and immunofluorescence analyses showing that TMEM55B interacts with many proteins that participate in mTORC1 activation including components of the vacuolar-type proton ATPase (V-ATPase) and Ragulator complexes at the lysosomal membrane. The amino acid-induced phosphorylation of the mTORC1 substrates S6K and 4E-BP was attenuated in TMEM55B-depleted cells compared with control cells. Depletion of TMEM55B was also found to evoke lysosomal stress as showed by translocation of the transcription factor TFEB to the nucleus. Furthermore, recruitment of the V1 domain subcomplex of V-ATPase to lipid rafts was abrogated in TMEM55B-depleted cells. Collectively, our results suggest that TMEM55B contributes to assembly of the V-ATPase complex in lipid rafts of the lysosomal membrane and to subsequent activation of mTORC1.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ATPasas de Translocación de Protón Vacuolares
/
Proteínas de Transporte Vesicular
/
Fosfoinosítido Fosfatasas
/
Diana Mecanicista del Complejo 1 de la Rapamicina
/
Aminoácidos
/
Lisosomas
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Genes Cells
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido