Lysosomal enzyme trafficking factor LYSET enables nutritional usage of extracellular proteins.
Science
; 378(6615): eabn5637, 2022 10 07.
Article
em En
| MEDLINE
| ID: mdl-36074822
ABSTRACT
Mammalian cells can generate amino acids through macropinocytosis and lysosomal breakdown of extracellular proteins, which is exploited by cancer cells to grow in nutrient-poor tumors. Through genetic screens in defined nutrient conditions, we characterized LYSET, a transmembrane protein (TMEM251) selectively required when cells consume extracellular proteins. LYSET was found to associate in the Golgi with GlcNAc-1-phosphotransferase, which targets catabolic enzymes to lysosomes through mannose-6-phosphate modification. Without LYSET, GlcNAc-1-phosphotransferase was unstable because of a hydrophilic transmembrane domain. Consequently, LYSET-deficient cells were depleted of lysosomal enzymes and impaired in turnover of macropinocytic and autophagic cargoes. Thus, LYSET represents a core component of the lysosomal enzyme trafficking pathway, underlies the pathomechanism for hereditary lysosomal storage disorders, and may represent a target to suppress metabolic adaptations in cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
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Doenças por Armazenamento dos Lisossomos
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Complexo de Golgi
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Lisossomos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article