ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
Control of Rab7a activity and localization through endosomal type Igamma PIP 5-kinase is required for endosome maturation and lysosome function.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. 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, 20 citations in OpenAlex.
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- Synaptojanin1 regulates synaptic dopamine release and axonal integrity via retromer-dependent endosomal sorting.Research square · 2026Article
- Extracellular vesicle engineering using a small scaffold protein.Nature communications · 2026Article
- Lysosomal swelling triggers LRRK2 activity.bioRxiv : the preprint server for biology · 2025Article
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Methamphetamine and Methamphetamine-Induced Neuronal Exosomes Modulate the Activity of Rab7a via PTEN to Exert an Influence on the Disordered Autophagic Flux Induced in Neurons.International journal of molecular sciences · 2025Article
- The space-time continuum in neurological disorders of the autophagosome-lysosome fusion machinery.Autophagy reports · 2025Review
- Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls cell sensitivity to interferon.Developmental cell · 2024Article
- PIP5K1C phosphoinositide kinase deficiency distinguishes PIKFYVE-dependent cancer cells from non-malignant cells.Autophagy · 2023Article
- CaAdvances in experimental medicine and biology · 2023Article
- Integrative clinical and molecular characterization of translocation renal cell carcinoma.Cell reports · 2022Article
- The roles of GTPase-activating proteins in regulated cell death and tumor immunity.Journal of hematology & oncology · 2021Review
- An Emerging Role for Phosphoinositides in the Pathophysiology of Parkinson's Disease.Journal of Parkinson's disease · 2021Review
- Emerging roles of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate as regulators of multiple steps in autophagy.Journal of biochemistry · 2020Review
- The secreted protein kinase CstK fromThe Journal of biological chemistry · 2020Article
- Phosphatidylinositol 4,5-bisphosphate in the Control of Membrane Trafficking.International journal of biological sciences · 2020Review
- Membrane Heterogeneity Controls Cellular Endocytic Trafficking.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The small GTPase Ras-related protein Rab-7a (Rab7a) serves as a key organizer of the endosomal-lysosomal system. However, molecular mechanisms controlling Rab7a activation levels and subcellular translocation are still poorly defined. Here, we demonstrate that type Igamma phosphatidylinositol phosphate 5-kinase i5 (PIPKIγi5), an endosome-localized enzyme that produces phosphatidylinositol 4,5-bisphosphate, directly interacts with Rab7a and plays critical roles in the control of the endosomal-lysosomal system. The loss of PIPKIγi5 blocks Rab7a recruitment to early endosomes, which prevents the maturation of early to late endosomes. PIPKIγi5 loss disturbs retromer complex connection with Rab7a, which blocks the retrograde sorting of Cation-independent Mannose 6-Phosphate Receptor from late endosomes. This leads to the decreased sorting of hydrolases to lysosomes and reduces the autophagic degradation. By modulating the retromer-Rab7a connection, PIPKIγi5 is also required for the recruitment of the GTPase-activating protein TBC1 domain family member 5 to late endosomes, which controls the conversion of Rab7a from the active state to the inactive state. Thus, PIPKIγi5 is critical for the modulation of Rab7a activity, localization, and function in the endosomal-lysosomal system.
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Registered trials
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.