Vinexin contributes to autophagic decline in brain ageing across species.

Park, So Jung; Frake, Rebecca A; Karabiyik, Cansu; Son, Sung Min; Siddiqi, Farah H; Bento, Carla F; Sterk, Peter; Vicinanza, Mariella; Pavel, Mariana; Rubinsztein, David C

Park, So Jung; Frake, Rebecca A; Karabiyik, Cansu; Son, Sung Min; Siddiqi, Farah H; Bento, Carla F; Sterk, Peter; Vicinanza, Mariella; Pavel, Mariana; Rubinsztein, David C.

Afiliación

Park SJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Frake RA; UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK.
Karabiyik C; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Son SM; UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK.
Siddiqi FH; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Bento CF; UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK.
Sterk P; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Vicinanza M; UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK.
Pavel M; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Rubinsztein DC; UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK.

Cell Death Differ ; 29(5): 1055-1070, 2022 05.

Article en En | MEDLINE | ID: mdl-34848853

RESUMEN

Autophagic decline is considered a hallmark of ageing. The activity of this intracytoplasmic degradation pathway decreases with age in many tissues and autophagy induction ameliorates ageing in many organisms, including mice. Autophagy is a critical protective pathway in neurons and ageing is the primary risk factor for common neurodegenerative diseases. Here, we describe that autophagosome biogenesis declines with age in mouse brains and that this correlates with increased expression of the SORBS3 gene (encoding vinexin) in older mouse and human brain tissue. We characterise vinexin as a negative regulator of autophagy. SORBS3 knockdown increases F-actin structures, which compete with YAP/TAZ for binding to their negative regulators, angiomotins, in the cytosol. This promotes YAP/TAZ translocation into the nucleus, thereby increasing YAP/TAZ transcriptional activity and autophagy. Our data therefore suggest brain autophagy decreases with age in mammals and that this is likely, in part, mediated by increasing levels of vinexin.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales; Proteínas Musculares; Factores de Transcripción; Proteínas Adaptadoras Transductoras de Señales/genética; Proteínas Adaptadoras Transductoras de Señales/metabolismo; Envejecimiento/genética; Animales; Autofagia/genética; Encéfalo/metabolismo; Humanos; Mamíferos/metabolismo; Ratones; Proteínas Musculares/genética; Proteínas Musculares/metabolismo; Fosfoproteínas/metabolismo; Factores de Transcripción/genética; Factores de Transcripción/metabolismo; Proteínas Señalizadoras YAP

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Adaptadoras Transductoras de Señales / Proteínas Musculares Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Cell Death Differ Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido

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