Juvenile hormone promotes paracellular transport of yolk proteins via remodeling zonula adherens at tricellular junctions in the follicular epithelium

Abstract

Juvenile hormone (JH) acts as a gonadotrophic hormone stimulating insect vitellogenesis and oogenesis. Paracellular transport of yolk proteins through intercellular channels (patency) in the follicular epithelium is a developmentally regulated and evolutionarily conserved process during vitellogenesis. However, the mechanisms underlying patency opening are poorly understood. Using the migratory locust Locusta migratoria as a model system, we report here that JH-regulated remodeling of zonula adherens (ZA), the belt-like adherens junction maintaining physical linking between follicle cells controlled the opening of patency. JH triggered phosphorylation of Partitioning defective protein 3 (Par3) via a signaling cascade including G protein-coupled receptor (GPCR), small GTPase Cell division cycle 42 (Cdc42) and atypical Protein kinase C (aPKC). Par3 phosphorylation resulted in its disassociation from β-Catenin, the cytoplasmic partner of ZA core component E-Cadherin. Release of Par3 from the β-Catenin/E-Cadherin complex caused ZA disassembly at tricellular contacts, consequently leading to patency enlargement. This study provides new insight into how JH stimulates insect vitellogenesis and egg production via inducing the opening of paracellular route for vitellogenin transport crossing the follicular epithelium barrier. Vitellogenesis is one of the most emblematic processes in female reproduction of oviparous animals. In many insects, the yolk protein precursor, vitellogenin (Vg) is synthesized in the fat body and transported to oocytes through the intercellular spaces (patency) among follicular cells. Juvenile hormone (JH), the arthropod-specific sesquiterpenoid plays a crucial role in paracellular Vg transport, but the molecular mechanisms of JH-stimulated patency remain elusive. In the present study, we show that JH acts via the GPCR-Cdc42-aPKC signaling cascade that triggers the phosphorylation of Par3, a critical scaffold protein of zonula adherens. JH-dependent Par3 phosphorylation results in its dissociation from the β-Catenin/E-Cadherin complex, consequently leading to patency opening for Vg transport. The findings reveal an important mechanism by which JH induces the remodeling of zonula adherens for the opening of paracellular route for Vg transport crossing the follicular epithelium barrier in the ovary.