Inhibition of lipid kinase PIKfyve reveals a role for phosphatase Inpp4b in the regulation of PI(3)P-mediated lysosome dynamics through VPS34 activity
Golam T. Saffi, Cheng An Wang, Emily M. Mangialardi, Jean Vacher, Roberto J. Botelho, Leonardo Salmena
Abstract
H-myo-inositol labeled PtdIns and PtdIns immunofluorescence staining, we observed that lysosomal PtdIns(3)P levels were significantly elevated in Inpp4b-deficient cells due to the hyperactivation of phosphatidylinositol 3-kinase catalytic subunit VPS34 enzymatic activity. In conclusion, our study identifies a novel signaling axis that maintains normal lysosomal homeostasis and dynamics, which includes the catalytic functions of Inpp4b, PIKfyve, and VPS34.
Topics & Concepts
LysosomeEndocytic cycleCell biologyPhosphataseAutophagyAutophagosomeBiologyPhosphatidylinositolKinasePhosphorylationBiochemistryEndocytosisCellEnzymeApoptosisAutophagy in Disease and TherapyCellular transport and secretionCalcium signaling and nucleotide metabolism