Juvenile Hormone Differentially Regulates Two Grp78 Genes Encoding Protein Chaperones Required for Insect Fat Body Cell Homeostasis and Vitellogenesis

Juvenile Hormone Differentially Regulates Two Grp78 Genes Encoding Protein Chaperones Required for Insect Fat Body Cell Homeostasis and Vitellogenesis

作者：Luo MW, Li D, Wang ZM, Guo W, Kang L, Zhou ST.

刊名：JOURNAL OF BIOLOGICAL CHEMISTRY；

年卷页码：292,8823-8834；

网联：http://www.jbc.org/content/292/21/8823

Abstract

Juvenile hormone (JH) has a well known role in stimulating insect vitellogenesis (i.e. yolk deposition) and oocyte maturation, but the molecular mechanisms of JH action in insect reproduction are unclear. The 78-kDa glucose-regulated protein (Grp78) is a heat shock protein 70-kDa family member and one of the most abundant chaperones in the endoplasmic reticulum (ER) where it helps fold newly synthesized peptides. Because of its prominent role in protein folding, and also ER stress, we hypothesized that Grp78 might be involved in fat body cell homeostasis and vitellogenesis and a regulatory target of JH. We report here that the migratory locust Locusta migratoriapossesses two Grp78 genes that are differentially regulated by JH. We found thatGrp78-1 is regulated by JH through Mcm4/7-dependent DNA replication and polyploidization, whereas Grp78-2 expression is directly activated by the JH-receptor complex comprising methoprene-tolerant and Taiman proteins. Interestingly, Grp78-2expression in the fat body is about 10-fold higher than that of Grp78-1. Knockdown of either Grp78-1 or Grp78-2 significantly reduced levels of vitellogenin (Vg) protein, accompanied by retarded maturation of oocytes. Depletion of both Grp78-1 and Grp78-2 resulted in ER stress and apoptosis in the fat body and in severely defective Vg synthesis and oocyte maturation. These results indicate a crucial role of Grp78 in JH-dependent vitellogenesis and egg production. The presence and differential regulation of two Grp78 genes in L. migratoria likely help accelerate the production of this chaperone in the fat body to facilitate folding of massively synthesized Vg and other proteins.