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Publication : PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following Engulfment.

First Author  Krishna S Year  2016
Journal  Dev Cell Volume  38
Issue  5 Pages  536-47
PubMed ID  27623384 Mgi Jnum  J:289081
Mgi Id  MGI:6436407 Doi  10.1016/j.devcel.2016.08.001
Citation  Krishna S, et al. (2016) PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following Engulfment. Dev Cell 38(5):536-47
abstractText  The scavenging of extracellular macromolecules by engulfment can sustain cell growth in a nutrient-depleted environment. Engulfed macromolecules are contained within vacuoles that are targeted for lysosome fusion to initiate degradation and nutrient export. We have shown that vacuoles containing engulfed material undergo mTORC1-dependent fission that redistributes degraded cargo back into the endosomal network. Here we identify the lipid kinase PIKfyve as a regulator of an alternative pathway that distributes engulfed contents in support of intracellular macromolecular synthesis during macropinocytosis, entosis, and phagocytosis. We find that PIKfyve regulates vacuole size in part through its downstream effector, the cationic transporter TRPML1. Furthermore, PIKfyve promotes recovery of nutrients from vacuoles, suggesting a potential link between PIKfyve activity and lysosomal nutrient export. During nutrient depletion, PIKfyve activity protects Ras-mutant cells from starvation-induced cell death and supports their proliferation. These data identify PIKfyve as a critical regulator of vacuole maturation and nutrient recovery during engulfment.
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