Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 293, Issue 5, Pages 1526-1535Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.R117.000629
Keywords
phosphatidylinositol; phosphatidylinositol kinase (PI Kinase); phosphatidylinositol phosphatase; phosphatidylinositol signaling; autophagy; endocytosis; endosome; lysosome; mTOR complex (mTORC)
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Funding
- Deutsche Forschungsgemeinschaft [SFB 740/TP C08, TRR 186/TP A08]
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Phosphoinositides (PIs) are phospholipids that perform crucial cell functions, ranging from cell migration and signaling to membrane trafficking, by serving as signposts of compartmental membrane identity. Although phosphatidylinositol 4,5-bisphosphate, 3-phosphate, and 3,5-bisphosphate are commonly considered as hallmarks of the plasma membrane, endosomes, and lysosomes, these compartments contain other functionally important PIs. Here, we review the roles of PIs in different compartments of the endolysosomal system in mammalian cells and discuss the mechanisms that spatiotemporally control PI conversion in endocytosis and endolysosomal membrane dynamics during endosome maturation and sorting. As defective PI conversion underlies human genetic diseases, including inherited myopathies, neurological disorders, and cancer, PI-converting enzymes represent potential targets for drug-based therapies.
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