Increased SORBS3 expression in brain ageing contributes to autophagic decline via YAP1-WWTR1/TAZ signaling

Autor:	Park, So Jung, Frake, Rebecca A, Rubinsztein, David C
Přispěvatelé:	Rubinsztein, David [0000-0001-5002-5263], Apollo - University of Cambridge Repository
Rok vydání:	2022
Předmět:	Aging Intracellular Signaling Peptides and Proteins Brain Cell Biology SORBS3 Mice Transcriptional Coactivator with PDZ-Binding Motif Proteins vinexin Autophagy Trans-Activators YAP1-WWTR1/TAZ Animals Humans brain aging Molecular Biology Adaptor Proteins Signal Transducing
Zdroj:	Autophagy. 19:943-944
ISSN:	1554-8635 1554-8627
DOI:	10.1080/15548627.2022.2100106
Popis:	Impaired autophagosome formation and reduced flux through the macroautophagy/autophagy pathway occurs outside the brain as part of normal aging in various species. We recently identified autophagic decline in mouse brain tissue dependent on aging. This sits alongside significantly increased expression of the Sorbs3/SORBS3/vinexin (sorbin and SH3 domain containing 3) gene in older mouse and human brains. We found that SORBS3 negatively regulates autophagy in several cell lines, including mouse primary neurons. SORBS3 depletion increases F-actin structures, which compete with YAP1-WWTR1/TAZ to bind AMOT (angiomotin) proteins in the cytosol. Unbound YAP1-WWTR1/TAZ is free to move into the nucleus and upregulate YAP1-WWTR1/TAZ target gene expression. This upregulates autophagosome formation, in part through increased expression of myosin- and actin-related genes. Moreover, we have shown these YAP1-WWTR1/TAZ target genes are downregulated in older mouse and human brains. Taken together, our findings suggest that increased SORBS3 expression contributes to autophagic decline in normal brain aging across species.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e0e2033704956fd3e5d5c1bfe9542c9 https://doi.org/10.1080/15548627.2022.2100106 Zobrazit plný text záznamu