ArticleProceedings of the National Academy of Sciences of the United States of America2024
Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed.
- DFCP1-containing ER microdomains mediate lysosomal membrane repair.Nature cell biology · 2026Article
- Endolysosomal inhibition uncouples tau uptake from intracellular seeding.The Journal of biological chemistry · 2026Article
- Article
- Astrocytes mobilize a broader repertoire of lysosomal repair mechanisms than neurons.iScience · 2026Article
- Glycoprotein-induced phase separation drives unconventional secretion of galectin-3.Nature communications · 2026Article
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Article
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- The ALS- and FTD-associated proteins annexin A11 and CHMP2B act sequentially in plasma membrane repair.Developmental cell · 2026Article
- Structural Mechanism and Cellular Restriction of Tau Seeding from Endolysosomes.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial protein import stress causes lysosomal damage and progressive tissue atrophy.EMBO reports · 2026Article
- ESCRT-III function in membrane fission and repair.Nature reviews. Molecular cell biology · 2026Review
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- IR-AMES uncovers structure and composition of Alzheimer's tau oligomers.bioRxiv : the preprint server for biology · 2026Article
- Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes.bioRxiv : the preprint server for biology · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Lysosome trafficking across intracellular and intercellular networks in the brain.Frontiers in molecular neuroscience · 2026Article
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7 authors.
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Abstract
The prion-like spread of protein aggregates is a leading hypothesis for the propagation of neurofibrillary lesions in the brain, including the spread of tau inclusions associated with Alzheimer's disease. The mechanisms of cellular uptake of tau seeds and subsequent nucleated polymerization of cytosolic tau are major questions in the field, and the potential for coupling between the entry and nucleation mechanisms has been little explored. We found that in primary astrocytes and neurons, endocytosis of tau seeds leads to their accumulation in lysosomes. This in turn leads to lysosomal swelling, deacidification, and recruitment of ESCRT proteins, but not Galectin-3, to the lysosomal membrane. These observations are consistent with nanoscale damage of the lysosomal membrane. Live cell imaging and STORM superresolution microscopy further show that the nucleation of cytosolic tau occurs primarily at the lysosome membrane under these conditions. These data suggest that tau seeds escape from lysosomes via nanoscale damage rather than wholesale rupture and that nucleation of cytosolic tau commences as soon as tau fibril ends emerge from the lysosomal membrane.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.