ArticleMolecular biology of the cell2006
The phosphoinositide kinase PIKfyve/Fab1p regulates terminal lysosome maturation in Caenorhabditis elegans.
Article in Molecular biology of the cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 132 citations in OpenAlex.
- PIKfyve is required for efficient phagosomal Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes.Journal of cell science · 2026Article
- An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.The Journal of cell biology · 2025Article
- Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve Is a Therapeutic Strategy for Pancreatic Cancer.Cancer research · 2025Article
- Actin dynamics switches two distinct modes of endosomal fusion in yolk sac visceral endoderm cells.eLife · 2024Article
- De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane.The Journal of cell biology · 2024Article
- Article
- A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes.The Journal of cell biology · 2023Article
- A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector.Autophagy · 2023Article
- Regulation of phosphoinositide metabolism in Apicomplexan parasites.Frontiers in cell and developmental biology · 2023Review
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- Linkage mapping reveals loci that underlie differences in Caenorhabditis elegans growth.G3 (Bethesda, Md.) · 2022Article
- The vacuolar morphology protein VAC14 plays an important role in sexual development in the filamentous ascomycete Sordaria macrospora.Current genetics · 2022Article
- Unraveling and targeting RAS-driven metabolic signaling for therapeutic gain.Advances in cancer research · 2022Review
- Condition-dependent functional shift of twoAutophagy · 2021Article
- A novel phosphoinositide kinase Fab1 regulates biosynthesis of pathogenic aflatoxin inVirulence · 2021Article
- Lysosome biogenesis: Regulation and functions.The Journal of cell biology · 2021Review
- Loss of PIKfyve Causes Transdifferentiation ofFrontiers in cell and developmental biology · 2021Article
- Roles for a lipid phosphatase in the activation of its opposing lipid kinase.Molecular biology of the cell · 2020Article
- Lysosomal size matters.Traffic (Copenhagen, Denmark) · 2020Review
- The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation.The Journal of cell biology · 2019Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Membrane dynamics is necessary for cell homeostasis and signal transduction and is in part regulated by phosphoinositides. Pikfyve/Fab1p is a phosphoinositide kinase that phosphorylates phosphatidylinositol 3-monophosphate into phosphatidylinositol-3,5-bisphosphate [PtdIns(3,5)P2] and is implicated in membrane homeostasis in yeast and in mammalian cells. These two phosphoinositides are substrates of myotubularin phosphatases found mutated in neuromuscular diseases. We studied the roles of phosphatidylinositol phosphate kinase 3 (PPK-3), the orthologue of PIKfyve/Fab1p, in a multicellular organism, Caenorhabditis elegans. Complete loss of ppk-3 function induces developmental defects characterized by embryonic lethality, whereas partial loss of function leads to growth retardation. At the cellular level, ppk-3 mutants display a striking enlargement of vacuoles positive for lysosome-associated membrane protein 1 in different tissues. In the intestine, RAB-7-positive late endosomes are also enlarged. Membranes of the enlarged lysosomes originate at least in part from smaller lysosomes, and functional and genetic analyses show that the terminal maturation of lysosomes is defective. Protein degradation is not affected in the hypomorphic ppk-3 mutant and is thus uncoupled from membrane retrieval. We measured the level of PtdIns(3,5)P2 and showed that its production is impaired in this mutant. This work strongly suggests that the main function of PPK-3 is to mediate membrane retrieval from matured lysosomes through regulation of PtdIns(3,5)P2.
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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.