The vitellogenin receptor functionality of the migratory locust depends on its phosphorylation by juvenile hormone.

Vitellogenin receptor (VgR) plays a pivotal role in ovarian vitellogenin (Vg) uptake and vertical transmission of pathogenic microbes and symbionts. However, the regulatory mechanisms of VgR action as an endocytic receptor and translocation from oocyte cytoplasm to the membrane remain poorly understood. Here, by using the migratory locust as a model system, we report that juvenile hormone (JH) promotes VgR phosphorylation at Ser in the second EGF-precursor homology domain. A signaling cascade including GPCR, PLC, extracellular calcium, and PKC-ι is involved in JH-stimulated VgR phosphorylation. This posttranslational regulation is a prerequisite for VgR binding to Vg on the external surface of the oocyte membrane and subsequent VgR/Vg endocytosis. Acidification, a condition in endosomes, induces VgR dephosphorylation along with the dissociation of Vg from VgR. Phosphorylation modification is also required for VgR recycling from oocyte cytoplasm to the membrane. Additionally, VgR phosphorylation and its requirement for Vg uptake and VgR recycling are evolutionarily conserved in other representative insects including the cockroach and the cotton bollworm This study fills an important knowledge gap of low-density lipoprotein receptors in posttranslational regulation, endocytosis, and intracellular recycling.