ArticleMolecular biology of the cell2024
Loss of the HOPS complex disrupts early-to-late endosome transition, impairs endosomal recycling and induces accumulation of amphisomes.
Article in Molecular biology of the cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- VPS33A and VPS18 orchestrate porcine epidemic diarrhea virus replication by modulating autophagic flux.Virulence · 2026Article
- Biallelic VPS41 Variants in Autosomal Recessive Spinocerebellar Ataxia 29 Resolved by Long-Read Sequencing and RNA Analysis.Molecular genetics & genomic medicine · 2026Article
- Late Endosome Transport by RILP-RAB7A Promotes Dendrite Arborization Independently of Degradation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Endosomes as central hubs of interorganellar communication and cellular homeostasis.Protein & cell · 2026Review
- Microvesicles, exosomes and their combinations with cytoplasmic organelles: from their discovery to their innovative roles in clinical medicine.Biology direct · 2026Review
- NPC1 trafficking via VPS41-dependent LAMP carriers regulates endosomal cholesterol homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Late endosome transport by RILP-RAB7A promotes dendrite arborization.bioRxiv : the preprint server for biology · 2025Article
- Neuropathy-associated Tecpr2 mutation knock-in mice reveal endolysosomal loss of function phenotypes in neurons and microglia.Cell death & disease · 2025Article
- Article
- The biophysical requirements that govern the efficient endosomal escape of designed mini-proteins.Nature chemistry · 2025Article
- Fighting RNA viruses with a gold nanoparticle Cas13d gene-editing armor.Molecular therapy. Nucleic acids · 2025Article
- Endocytic tethers modulate unconventional GAPDH secretion.Cell surface (Amsterdam, Netherlands) · 2025Article
- Parkin-dependent ubiquitination of TAX1BP1 directs efficient autophagic removal of defective mitochondria.bioRxiv : the preprint server for biology · 2025Article
- VPS41 recruits biosynthetic LAMP-positive vesicles through interaction with Arl8b.The Journal of cell biology · 2025Article
- VPS18 contributes to phagosome membrane integrity inScience advances · 2025Article
- An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal.Autophagy · 2024Article
- CORVET-specific subunit levels determine the balance between HOPS/CORVET endosomal tethering complexes.Scientific reports · 2024Article
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The multisubunit HOPS tethering complex is a well-established regulator of lysosome fusion with late endosomes and autophagosomes. However, the role of the HOPS complex in other stages of endo-lysosomal trafficking is not well understood. To address this, we made HeLa cells knocked out for the HOPS-specific subunits Vps39 or Vps41, or the HOPS-CORVET-core subunits Vps18 or Vps11. In all four knockout cells, we found that endocytosed cargos were trapped in enlarged endosomes that clustered in the perinuclear area. By correlative light-electron microscopy, these endosomes showed a complex ultrastructure and hybrid molecular composition, displaying markers for early (Rab5, PtdIns3P, EEA1) as well as late (Rab7, CD63, LAMP1) endosomes. These "HOPS bodies" were not acidified, contained enzymatically inactive cathepsins and accumulated endocytosed cargo and cation-independent mannose-6-phosphate receptor (CI-MPR). Consequently, CI-MPR was depleted from the TGN, and secretion of lysosomal enzymes to the extracellular space was enhanced. Strikingly, HOPS bodies also contained the autophagy proteins p62 and LC3, defining them as amphisomes. Together, these findings show that depletion of the lysosomal HOPS complex has a profound impact on the functional organization of the entire endosomal system and suggest the existence of a HOPS-independent mechanism for amphisome formation.
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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.