Rag GTPases and phosphatidylinositol 3-phosphate mediate recruitment of the AP-5/SPG11/SPG15 complex.
J Cell Biol
; 220(2)2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-33464297
ABSTRACT
Adaptor protein complex 5 (AP-5) and its partners, SPG11 and SPG15, are recruited onto late endosomes and lysosomes. Here we show that recruitment of AP-5/SPG11/SPG15 is enhanced in starved cells and occurs by coincidence detection, requiring both phosphatidylinositol 3-phosphate (PI3P) and Rag GTPases. PI3P binding is via the SPG15 FYVE domain, which, on its own, localizes to early endosomes. GDP-locked RagC promotes recruitment of AP-5/SPG11/SPG15, while GTP-locked RagA prevents its recruitment. Our results uncover an interplay between AP-5/SPG11/SPG15 and the mTORC1 pathway and help to explain the phenotype of AP-5/SPG11/SPG15 deficiency in patients, including the defect in autophagic lysosome reformation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
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Proteínas de Transporte
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Fosfatos de Fosfatidilinositol
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Proteínas Monoméricas de Ligação ao GTP
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Proteínas Adaptadoras de Transporte Vesicular
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Complexos Multiproteicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article