Endocytic turnover of the plasma membrane (PM) is crucial for its accurate composition and function, and endocytotic removal of PM proteins is a key mechanism for turnover. Photoreceptors are sensory neurons with an apical plasma membrane, which contain the G-protein-coupled receptor rhodopsin (Rh1) to absorb photons and to initiate phototransduction. After photon absorption, Rh1 is phosphorylated and removed from the plasma membrane by clathrin-mediated endocytosis (CME) to a Rab5-labelled compartment for recycling or degradation. Now, on page 2119, Padinjat Raghu and colleagues identify phosphatidylinositol 5-phosphate 4-kinase (PIP4K) as a new regulator of CME in Drosophila. A loss-of-function mutant for PIP4K results in expanded endomembranes into the cell body that contain Rh1-loaded vesicles. The authors show that the mutant phenotype is suppressed when Rab5 is downregulated, which suggests a Rab5-dependent expansion of endomembranes in cells that lack PIP4K. Further, when PIP4K is targeted to early endosomal compartments, but not the PM, the accumulation of Rh1-loaded vesicles in mutants is rescued. Interestingly, by using Drosophila cell culture and a canonical endocytotic cargo, the authors demonstrate that loss of PIP4K also increases CME in S2 cells. Taken together, this study establishes PIP4K as a regulator of endosomal dynamics during CME by potentially controlling parts of the core machinery of early endosome homeostasis in cells.
