Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics during clathrin-mediated endocytosis

Journal of Cell Science
Kumari KamaleshPadinjat Raghu

Abstract

Endocytic turnover is essential for the regulation of the protein composition and function of the plasma membrane, and thus affects the plasma membrane levels of many receptors. In Drosophila melanogaster photoreceptors, photon absorption by the G-protein-coupled receptor (GPCR) rhodopsin 1 (Rh1; also known as NinaE) triggers its endocytosis through clathrin-mediated endocytosis (CME). We find that CME of Rh1 is regulated by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Flies lacking PIP4K show mislocalization of Rh1 on expanded endomembranes within the cell body. This mislocalization of Rh1 was dependent on the formation of an expanded Rab5-positive compartment. The Rh1-trafficking defect in PIP4K-depleted cells could be suppressed by downregulating Rab5 function or by selectively reconstituting PIP4K in the PI3P-enriched early endosomal compartment of photoreceptors. We also found that loss of PIP4K was associated with increased CME and an enlarged Rab5-positive compartment in cultured Drosophila cells. Collectively, our findings define PIP4K as a novel regulator of early endosomal homeostasis during CME.

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Citations

Jul 13, 2019·Journal of Cell Science·Yuna OtsukaAkiko K Satoh
Oct 28, 2019·Bioscience Reports·Avishek GhoshPadinjat Raghu
May 26, 2020·The Journal of Comparative Neurology·Evan K NochLewis C Cantley
Sep 12, 2019·Frontiers in Molecular Neuroscience·Padinjat RaghuSankhanil Saha
Jul 25, 2019·Frontiers in Cell and Developmental Biology·Zinia D'SouzaVladimir V Lupashin
Mar 8, 2021·Current Opinion in Cell Biology·Padinjat Raghu
Jun 15, 2021·Frontiers in Molecular Biosciences·Jatin BehariVasudevan Seshadri

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