Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors

摘要

In the anautogenous disease vector mosquitoes Anopheles gambiae and Aedes aegypti, egg development is nutritionally controlled. A blood meal permits further maturation of developmentally repressed previtellogenic egg chambers. This entails massive storage of extraovarian yolk precursors by the oocyte, which occurs through a burst of clathrin-mediated endocytosis. Yolk precursors are concentrated at clathrin-coated structures on the oolemma by two endocytic receptors, the vitellogenin and lipophorin receptors. Both these mosquito receptors are members of the low-density-lipoprotein-receptor superfamily that contain FxNPxY-type internalization signals. In mammals, this tyrosine-based signal is not decoded by the endocytic AP-2 adaptor complex directly. Instead, two functionally redundant phosphotyrosine-binding domain adaptors, Disabled 2 and the autosomal recessive hypercholesterolemia protein (ARH) manage the internalization of the FxNPxY sorting signal. Here, we report that a mosquito ARH-like protein, which we designate trephin, possess similar functional properties to the orthologous vertebrate proteins despite engaging AP-2 in an atypical manner, and that mRNA expression in the egg chamber is strongly upregulated shortly following a blood meal. Temporally regulated trephin transcription and translation suggests a mechanism for controlling yolk uptake when vitellogenin and lipophorin receptors are expressed and clathrin coats operate in previtellogenic ovaries.