title: Internalization of LDL-receptor superfamily yolk-protein receptors during mosquito oogenesis involves transcriptional regulation of PTB-domain adaptors.
abstract: 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.
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Mishra
authors.forename: Anupma
authors.initials: A
authors.lastname: Jha
authors.forename: Amie L
authors.initials: AL
authors.lastname: Steinhauser
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kokoza
authors.forename: Charles H
authors.initials: CH
authors.lastname: Washabaugh
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Raikhel
authors.forename: Woodbridge A
authors.initials: WA
authors.lastname: Foster
authors.forename: Linton M
authors.initials: LM
authors.lastname: Traub
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D009033:Culicidae / Q000502:physiology*; D004705:Endocytosis; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009866:Oogenesis; D011973:Receptors, LDL / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D011973:Receptors, LDL