ArticleBiological psychiatry2022
BAG3 Regulation of RAB35 Mediates the Endosomal Sorting Complexes Required for Transport/Endolysosome Pathway and Tau Clearance.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.American journal of physiology. Cell physiology · 2026Article
- A Bioinformatic Analysis of BAG Protein Interactors and Pathways in Alzheimer's and Parkinson's Disease.Journal of molecular neuroscience : MN · 2026Review
- BAG3 modulates clathrin-mediated endocytosis and tau uptake in astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Genetic and proteomic analysis identifies BAG3 as an amyloid-responsive regulator of neuronal proteostasis.Acta neuropathologica · 2025Article
- One BAG Does Not Fit All: Differences and Similarities of BAG Family Members in Mediating Central Nervous System Homeostasis.Biological psychiatry · 2025Review
- The role of small GTPases in Alzheimer's disease tau pathologies.Frontiers in cellular neuroscience · 2025Review
- BAG3's dual roles in Parkinson's disease and cardiomyopathy: benefit or liability?Acta neuropathologica · 2024Article
- Neuronal BAG3 attenuates tau hyperphosphorylation, synaptic dysfunction, and cognitive deficits induced by traumatic brain injury via the regulation of autophagy-lysosome pathway.Acta neuropathologica · 2024Article
- BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1.Autophagy · 2024Article
- Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
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- Commentary: BAG3 as a Mediator of Endosome Function and Tau Clearance.Neuroscience · 2023Review
- Upregulation of the ESCRT pathway and multivesicular bodies accelerates degradation of proteins associated with neurodegeneration.Autophagy reports · 2023Article
- Keeping synapses in shape: degradation pathways in the healthy and aging brain.Neuronal signaling · 2022Review
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
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Authors and funding
8 authors at 2 institutions in 1 country.
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Abstract
backgroundDeclining proteostasis with aging contributes to increased susceptibility to neurodegenerative diseases, including Alzheimer's disease (AD). Emerging studies implicate impairment of the endosome-lysosome pathway as a significant factor in the pathogenesis of these diseases. Previously, we demonstrated that BAG3 regulates phosphorylated tau clearance. However, we did not fully define how BAG3 regulates endogenous tau proteostasis, especially in the early stages of disease progression.
methodsMass spectrometric analyses were performed to identify neuronal BAG3 interactors. Multiple biochemical assays were used to investigate the BAG3-HSP70-TBC1D10B (EPI64B)-RAB35-HRS regulatory networks. Live-cell imaging was used to study the dynamics of the endosomal pathway. Immunohistochemistry and immunoblotting were performed in human AD brains and in P301S tau transgenic mice with BAG3 overexpressed.
resultsThe primary group of neuronal BAG3 interactors identified are involved in the endocytic pathway. Among them were key regulators of small GTPases, such as the RAB35 GTPase-activating protein TBC1D10B. We demonstrated that a BAG3-HSP70-TBC1D10B complex attenuates the ability of TBC1D10B to inactivate RAB35. Thus, BAG3 interacts with TBC1D10B to support the activation of RAB35 and recruitment of HRS, initiating endosomal sorting complex required for transport-mediated endosomal tau clearance. Furthermore, TBC1D10B shows significantly less colocalization with BAG3 in AD brains than in age-matched controls. Overexpression of BAG3 in P301S tau transgenic mice increased the colocalization of phosphorylated tau with the endosomal sorting complex required for transport III protein CHMP2B and reduced the levels of the mutant human tau.
conclusionsWe identified a novel BAG3-TBC1D10B-RAB35 regulatory axis that modulates endosomal sorting complex required for transport-dependent protein degradation machinery and tau clearance. Dysregulation of BAG3 could contribute to the pathogenesis of AD.
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