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La separación de fase de FUS es suprimida por su receptor de importación nuclear y la metilación de arginina
Mario Hofweber1, Saskia Hutten2, Benjamin Bourgeois3
1Biomedical Center (BMC), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany; Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians University of Munich, 82152 Planegg-Martinsried, Germany.
Cell
|April 21, 2018
Resumen
La metilación de la transportina y la arginina previene la agregación de la proteína FUS en la demencia frontotemporal (FTD) y la esclerosis lateral amiotrófica (ALS). Las interrupciones en estos procesos promueven la separación de la fase líquida de FUS y la asociación de gránulos de estrés, lo que contribuye a la neurodegeneración.
Área de la Ciencia:
- La neurociencia
- Biología molecular
- Biología celular
Sus antecedentes:
- Los agregados FUS citoplasmáticos son características patológicas clave en la demencia frontotemporal (FTD) y la esclerosis lateral amiotrófica (ALS).
- La importación nuclear de FUS, mediada por Transportin/Karyopherin-β2, está interrumpida en estas enfermedades neurodegenerativas.
- Las mutaciones en la señal de localización nuclear (NLS) de la ELA debilitan la unión de Transportin en pacientes con ELA-ELA.
- En el FTD-FUS, la agregación de transportina y la pérdida de metilación de arginina en el FUS interrumpen la interacción FUS-Transportina.
Objetivo del estudio:
- Investigar el papel de la metilación de la transportina y la arginina en la regulación del comportamiento de la proteína FUS.
- Comprender cómo las interrupciones en estos mecanismos reguladores contribuyen a la neurodegeneración asociada a la FUS.
Principales métodos:
- Investigó la función de la metilación de la transportina y la arginina en la supresión de la separación de fase de la FUS.
- Se analizó el impacto de las mutaciones FUS-NLS asociadas a la ELA en la actividad de chaperón de Transportin.
- Se examinó el efecto de la pérdida de metilación de arginina en la FUS sobre la separación de fase y la asociación de gránulos de tensión.
Principales resultados:
- La metilación de la transportina y la arginina suprime la separación de fase impulsada por RGG / RG y la asociación de gránulos de tensión de FUS.
- Las mutaciones FUS-NLS asociadas a la ELA debilitan la actividad acompañante de Transportin.
- La pérdida de metilación de la arginina FUS promueve la separación de fase FUS y la partición de gránulos de tensión.
Conclusiones:
- La metilación de la transportina y la arginina es crucial para mantener la homeostasis de la fase líquida de la FUS.
- Las interrupciones en estos mecanismos reguladores están implicadas en enfermedades neurodegenerativas asociadas a la FUS como FTD y ALS.
- Estos hallazgos revelan nuevos conocimientos sobre la patogénesis de la neurodegeneración relacionada con el SUS.
Palabras clave:
La ELADispositivos para el trabajo de la manoEn el caso de las carieferina-β2 (Kapβ2)Transporte (TNPO1)Metilación de la argininafusión en el sarcoma (FUS)neurodegeneraciónimportación de energía nuclearseparación de fasesgránulos de esfuerzoMás Videos Relacionados
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