Abstract
ABSTRACTEndocytic 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.
Highlights
The ability to sense and respond to changes in local milieu is fundamental to survival
Transmission electron microscopy (TEM) of retinae at 90% pupal development from PIP4K29 mutants reared under illumination revealed an increase in the number of vesicular endosome-like compartments (Fig. 1Bii,iii,iii′) as well as vesicles that were enlarged in size, in some cases as large as >1 μm2 (Fig. 1Biv)
rhodopsin 1 (Rh1) at the plasma membrane is subject to ongoing clathrindependent endocytic turnover, a process that is essential for normal apical domain development (Raghu et al, 2009)
Summary
The ability to sense and respond to changes in local milieu is fundamental to survival. The plasma membrane (PM) of a cell has a defined protein composition, including the specific numbers and types of receptors required to respond to environmental stimuli. The control of composition requires transport events that deliver proteins to the PM and tight control of endocytic processes that can remove proteins away from this membrane. The accurate control of PM membrane turnover through regulation of transport to and endocytosis from the PM is crucial for its composition and function. In the nervous systems of metazoans, stimulus detection occurs through sensory neurons, which are polarized cells with an apical PM whose composition is optimized for stimulus detection.
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