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

Significance During vitellogenesis of oviparous animals, vitellogenin receptor (VgR)–mediated endocytosis is crucial for the incorporation of yolk proteins into oocytes. VgR also serves as a gatekeeper for vertical transmission of pathogenic microbes and symbionts. Juvenile hormone (JH) acts as a gonadotrophic hormone and stimulates this process in many insect species, but the regulatory mechanisms remain elusive. We find that JH activates the GPCR-PLC-PKC-ι cascade and phosphorylates VgR in an EGF-precursor homology domain. Endosomal acidification leads to VgR dephosphorylation. Phosphorylation is essential for VgR to translocate from oocyte cytoplasm to the membrane to bind with vitellogenin on the membrane and to internalize vitellogenin in oocytes. Moreover, JH-promoted VgR phosphorylation for intracellular recycling and vitellogenin deposition is evolutionarily conserved across divergent insect orders.