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Characterization of Neuronal Lysosome Interactome with Proximity Labeling Proteomics
Published on: June 23, 2022
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El factor de tráfico de enzimas lisosomales LYSET permite el uso nutricional de las proteínas extracelulares
Catarina Pechincha1,2, Sven Groessl1,2, Robert Kalis3,4
1Cell Signaling and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Science (New York, N.Y.)
|September 8, 2022
Resumen
Las células de los mamíferos utilizan proteínas extracelulares para obtener aminoácidos, un proceso crucial para el crecimiento del cáncer. Los investigadores identificaron a LYSET (TMEM251) como esencial para el tráfico de enzimas lisosomales y la absorción de nutrientes, revelando su papel en el metabolismo del cáncer y los trastornos de almacenamiento lisosomal.
Área de la Ciencia:
- Biología celular
- Biología molecular
- La bioquímica
Sus antecedentes:
- Las células de los mamíferos pueden sintetizar aminoácidos a través de la macropinocitosis y la degradación lisosómica de las proteínas extracelulares.
- Las células cancerosas explotan esta vía para crecer en microambientes tumorales limitados en nutrientes.
Objetivo del estudio:
- Identificar las proteínas críticas para la utilización de proteínas extracelulares como fuente de aminoácidos.
- Para aclarar el mecanismo molecular de LYSET (TMEM251) en la adquisición de nutrientes celulares y la función lisosómica.
Principales métodos:
- Se realizaron pruebas genéticas en condiciones nutricionales definidas para identificar los genes esenciales.
- Se llevaron a cabo estudios de asociación de proteínas en el aparato de Golgi.
- Se evaluó la actividad enzimática lisosómica y la rotación de carga en células con deficiencia de LYSET.
Principales resultados:
- LYSET (TMEM251) fue identificado como una proteína transmembrana requerida selectivamente para el consumo de proteínas extracelulares.
- LYSET se asocia con la GlcNAc-1-fosfotransferasa en el Golgi, estabilizándola.
- La deficiencia de LYSET conduce al agotamiento de las enzimas lisosomales y al deterioro de la rotación de carga macropinocítica y autofágica.
Conclusiones:
- LYSET es un componente clave de la vía de tráfico de enzimas lisosomales.
- La disfunción de LYSET contribuye a la patología de los trastornos de almacenamiento lisosomal hereditarios.
- LYSET puede ser un objetivo terapéutico para inhibir las adaptaciones metabólicas en las células cancerosas.
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