2026-04-03 バージニア工科大学
Jinsong Zhu, professor in the Department of Biochemistry, examines mosquitoes in a petri dish inside the insectary. Zhu and his team discovered that a single protein controls mosquito reproduction by working in two places inside the cell. Photo by Marya Barlow for Virginia Tech.
<関連情報>
- https://news.vt.edu/articles/2026/03/cals-mosquito-reproduction-study.html
- https://www.pnas.org/doi/10.1073/pnas.2516796122
膜局在型METはPVRと結合し、ネッタイシマカにおける核外幼若ホルモンシグナル伝達を媒介する Membrane-localized MET engages PVR to mediate extranuclear juvenile hormone signaling in Aedes aegypti
Wenhao Zhao, Katara Griffith, Jiangtao Liang, +3 , and Jinsong Zhu
Proceedings of the National Academy of Sciences Published:November 13, 2025
DOI:https://doi.org/10.1073/pnas.2516796122
Significance
Juvenile hormone (JH) regulates insect development and reproduction through both intracellular and cell membrane–initiated signaling; however, the identity of the membrane receptor has remained unclear. Here, we show that in the fat body of adult female mosquitoes, Methoprene-tolerant (MET)—the well-established intracellular JH receptor—is also present on the cell membrane, where it functions specifically as a JH membrane receptor. On the membrane, MET interacts with the receptor tyrosine kinase PVR to activate downstream signaling cascades. Together, membrane- and nucleus-localized MET mediate dual modes of JH signaling, allowing this hormone to fine-tune physiological processes with enhanced versatility and precision. Elucidating this integrated mechanism may inform new strategies to disrupt mosquito reproduction and reduce disease transmission.
Abstract
Although Methoprene-tolerant (MET) is well established as the intracellular receptor mediating the genomic actions of juvenile hormone (JH) in insects, the identity of the receptor responsible for initiating extranuclear JH responses has remained elusive. In the yellow fever mosquito Aedes aegypti, we identify the platelet-derived growth factor- and vascular endothelial growth factor-receptor related (PVR) protein as a key mediator of membrane-initiated JH signaling. JH treatment induces robust PVR phosphorylation in the fat body of adult female mosquitoes. Disruption of PVR function suppresses JH-induced activation of the phospholipase C and phosphatidylinositol 3-kinase signaling pathways and impairs primary follicle growth during the previtellogenic stage. Strikingly, JH-induced PVR phosphorylation and downstream signaling require MET, specifically its ligand-binding activity, but not its DNA-binding domain. A subpopulation of MET localizes to the plasma membrane of fat body cells, where it physically interacts with PVR between 24 h postemergence and 24 h post–blood feeding, suggesting that membrane-localized MET functions as the extranuclear JH receptor. Transcriptomic analyses following RNA interference (RNAi)-mediated knockdown of Met or Pvr demonstrate that PVR broadly contributes to JH-regulated gene expression. Notably, PVR-dependent signaling modulates genes that are also regulated by nuclear MET and enables JH to regulate additional gene sets independently of MET-mediated transcriptional regulation. These findings uncover a previously unrecognized MET–PVR signaling axis and support an integrated model of JH action in which membrane and nuclear pathways cooperate to enhance the specificity and complexity of JH function during the previtellogenic phase in mosquitoes.

