Retromer regulates the lysosomal clearance of MAPT/tau.
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ABSTRACT:
SUBMITTER: Carosi JM
PROVIDER: S-EPMC8496733 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Retromer regulates the lysosomal clearance of MAPT/tau.
Carosi Julian M JM Hein Leanne K LK van den Hurk Mark M Adams Robert R Milky Bridget B Singh Sanjna S Bardy Cedric C Denton Donna D Kumar Sharad S Sargeant Timothy J TJ
Autophagy 20200922 9
The macroautophagy/autophagy-lysosome axis enables the clearance and degradation of cytoplasmic components including protein aggregates, damaged organelles and invading pathogens. Protein aggregation and lysosomal system dysfunction in the brain are common features of several late-onset neurological disorders including Alzheimer disease. Spatial overlap between depletion of the endosomal-sorting complex retromer and MAPT/tau aggregation in the brain have been previously reported. However, whethe ...[more]
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Project description:Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform the first integrated multiomics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify profound changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide an unprecedented integrated view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.
2023-04-17 | GSE223292 | GEO