Vinexin contributes to autophagic decline in brain ageing across species.
So Jung ParkRebecca A FrakeCansu KarabiyikSung Min SonFarah H SiddiqiCarla F BentoPeter SterkMariella VicinanzaMariana Pavel-TanasaDavid C RubinszteinPublished in: Cell death and differentiation (2021)
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.
Keyphrases
- cell death
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- transcription factor
- gene expression
- poor prognosis
- resting state
- white matter
- adipose tissue
- genome wide
- functional connectivity
- high resolution
- dna methylation
- long non coding rna
- mass spectrometry
- blood brain barrier
- subarachnoid hemorrhage
- big data
- insulin resistance
- heat shock