Commentary: BAG3 as a Mediator of Endosome Function and Tau Clearance

Lin, Heng; Deaton, Carol A.; Johnson, Gail V.W.

doi:10.1016/j.neuroscience.2022.05.002

Cited by 4 publications

(1 citation statement)

References 60 publications

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“…LC3C is often associated with processes like xenophagy and aggrephagy (24, 43). In both cases, the potential cargo may be unable to be ubiquitinated due to structural inaccessibility.BAG3 has not been implicated with xenophagic processes so far but is a very well recognized actor in aggrephagic processes (11, 44, 45). In this case, BAG3 does not necessarily recognize its cargo through ubiquitin binding, which makes it a possible mediator of ubiquitin independent autophagy (46).…”

Section: Discussionmentioning

confidence: 99%

Co-chaperone BAG3 directly target autophagic degradation via its LC3-interacting regions

Körschgen

Baeken

Schmitt

et al. 2023

Preprint

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The co-chaperone BAG3 is a hub for a variety of cellular pathways via its multiple domains and its interaction with HSP70 and HSPB8. Under aging and cellular stress conditions in particular, together with molecular chaperones, BAG3 ensures the sequestration of aggregated or aggregation prone ubiquitinated proteins to the autophagic-lysosomal system via ubiquitin receptors. There are emerging indications that BAG3-mediated selective macroautophagy also copes with non-ubiquitinated cargo. Phylogenetically, BAG3 comprises several highly conserved predicted LIRs, LC3-interacting regions, which might directly target BAG3 including its cargo to ATG8 proteins and directly drive their autophagic degradation. Based on pull-down experiments, peptide arrays and proximity ligation assays, our results provide evidence of an interaction of BAG3 with ATG8 proteins. In addition, we could demonstrate that mutations within the LIRs impair co-localization with ATG8 proteins in immunofluorescence. A BAG3 variant mutated in all LIRs results in a substantial decrease of BAG3 levels within purified native autophagic vesicles compared to wild-type BAG3. These results strongly suggest LC3-mediated sequestration of BAG3. Therefore, we conclude that in addition of being a key co-chaperone to HSP70, BAG3 may also act as cargo receptor for client proteins, which would significantly extend the role of BAG3 in selective macroautophagy and protein quality control.

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Section: Discussionmentioning

confidence: 99%

Co-chaperone BAG3 directly target autophagic degradation via its LC3-interacting regions

Körschgen

Baeken

Schmitt

et al. 2023

Preprint

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Editorial Special Issue Neuroscience “Tauopathies”

2023

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Alzheimer DataLENS: An Open Data Analytics Portal for Alzheimer’s Disease Research

Noori,

Jayakumar,

Moturi

et al. 2024

JAD

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Background: Recent Alzheimer’s disease (AD) discoveries are increasingly based on studies from a variety of omics technologies on large cohorts. Currently, there is no easily accessible resource for neuroscientists to browse, query, and visualize these complex datasets in a harmonized manner. Objective: Create an online portal of public omics datasets for AD research. Methods: We developed Alzheimer DataLENS, a web-based portal, using the R Shiny platform to query and visualize publicly available transcriptomics and genetics studies of AD on human cohorts. To ensure consistent representation of AD findings, all datasets were processed through a uniform bioinformatics pipeline. Results: Alzheimer DataLENS currently houses 2 single-nucleus RNA sequencing datasets, over 30 bulk RNA sequencing datasets from 19 brain regions and 3 cohorts, and 2 genome-wide association studies (GWAS). Available visualizations for single-nucleus data include bubble plots, heatmaps, and UMAP plots; for bulk expression data include box plots and heatmaps; for pathways include protein-protein interaction network plots; and for GWAS results include Manhattan plots. Alzheimer DataLENS also links to two other knowledge resources: the AD Progression Atlas and the Astrocyte Atlas. Conclusions: Alzheimer DataLENS is a valuable resource for investigators to quickly and systematically explore omics datasets and is freely accessible at https://alzdatalens.partners.org.

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Commentary: BAG3 as a Mediator of Endosome Function and Tau Clearance

Cited by 4 publications

References 60 publications

Co-chaperone BAG3 directly target autophagic degradation via its LC3-interacting regions

Co-chaperone BAG3 directly target autophagic degradation via its LC3-interacting regions

Editorial Special Issue Neuroscience “Tauopathies”

Alzheimer DataLENS: An Open Data Analytics Portal for Alzheimer’s Disease Research

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