ArticleThe Journal of biological chemistry2010
Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 129 citations in OpenAlex.
- Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation.Cell reports · 2026Article
- TBC1D15 functions as an Arl4D GAP and promotes the mitochondrial translocation of Arl4D for organelle homeostasis.Journal of cell science · 2026Article
- FIS1 dependent peripheral fission exacerbates mitochondrial fragmentation and dysfunction in prion diseases.Frontiers in neuroscience · 2026Article
- Rab7a is required to degrade select blood-brain barrier junctional proteins after ischemic stroke.Acta neuropathologica communications · 2025Article
- AP2A1 activates Rab7 to promote axonal autophagosome transport and slow the progression of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- TIGAR exacerbates obesity by triggering LRRK2-mediated defects in macroautophagy and chaperone-mediated autophagy in adipocytes.Autophagy · 2024Article
- The GTPase activating protein Gyp7 regulates Rab7/Ypt7 activity on late endosomes.The Journal of cell biology · 2024Article
- SARS-CoV-2 virulence factor ORF3a blocks lysosome function by modulating TBC1D5-dependent Rab7 GTPase cycle.Nature communications · 2024Article
- Endolysosomal trafficking controls yolk granule biogenesis in vitellogenic Drosophila oocytes.PLoS genetics · 2024Article
- Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.Frontiers in molecular neuroscience · 2024Review
- A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.Frontiers in physiology · 2024Review
- Article
- Misregulation of mitochondria-lysosome contact dynamics in Charcot-Marie-Tooth Type 2B disease Rab7 mutant sensory peripheral neurons.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A lysosome membrane regeneration pathway depends on TBC1D15 and autophagic lysosomal reformation proteins.Nature cell biology · 2023Article
- Lysosomal Ion Channels and Lysosome-Organelle Interactions.Handbook of experimental pharmacology · 2023Article
- Mid51/Fis1 mitochondrial oligomerization complex drives lysosomal untethering and network dynamics.The Journal of cell biology · 2022Article
- Mechanisms regulating the sorting of soluble lysosomal proteins.Bioscience reports · 2022Review
- Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases.Trends in neurosciences · 2022Review
- Vam6 reduces iNKT cell function in tumorFrontiers in immunology · 2022Article
- Mitochondria inter-organelle relationships in cancer protein aggregation.Frontiers in cell and developmental biology · 2022Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The small GTPase Rab7 promotes fusion events between late endosomes and lysosomes. Rab7 activity is regulated by extrinsic signals, most likely via effects on its guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP). Based on their homology to the yeast proteins that regulate the Ypt7 GTP binding state, TBC1D15, and mammalian Vps39 (mVps39) have been suggested to function as the Rab7 GAP and GEF, respectively. We developed an effector pull-down assay to test this model. TBC1D15 functioned as a Rab7 GAP in cells, reducing Rab7 binding to its effector protein RILP, fragmenting the lysosome, and conferring resistance to growth factor withdrawal-induced cell death. In a cellular context, TBC1D15 GAP activity was selective for Rab7. TBC1D15 overexpression did not inhibit transferrin internalization or recycling, Rab7-independent processes that require Rab4, Rab5, and Rab11 activation. TBC1D15 was thus renamed Rab7-GAP. Contrary to expectations for a Rab7 GEF, mVps39 induced lysosomal clustering without increasing Rab7 GTP binding. Moreover, a dominant-negative mVps39 mutant fragmented the lysosome and promoted growth factor independence without decreasing Rab7-GTP levels. These findings suggest that a protein other than mVps39 serves as the Rab7 GEF. In summary, although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence.
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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.