A proposed model for the regulation and function of two Grp78 genes in JH-stimulated locust vitellogenesis.
Grp78-1 is regulated by the JH-Met-Mcm4/7 pathway, whereas Grp78-2 is directly activated by the JH-receptor complex. The large amount of Grp78 in the ER facilitates the folding of massively synthesized Vg and other proteins and maintains cell homeostasis. Loss of Grp78 function induces ER stress, which activates the Ire1-dependent decay (RIDD) of mRNA and Perk-eIF2α pathway. RIDD results in the degradation of Vg mRNA. The activated eIF2α inhibits protein translation, leading to reduced synthesis of Vg and other regulatory proteins that directly or indirectly regulate Vg synthesis. Consequently, Vg in the fat body and ovary are substantially reduced, and the oocyte maturation and egg production are blocked.