Distinct vitellogenin domains differentially regulate immunological outcomes in invertebrates

J Biol Chem. 2021 Jan-Jun;296:100060. doi: 10.1074/jbc.RA120.015686. Epub 2020 Dec 1.


The classical role of Vitellogenin (Vg) is providing energy reserves for developing embryos, but its roles appear to extend beyond this nutritional function, and its importance in host immune defense is garnering increasing research attention. However, Vg-regulated immunological functions are dependent on three different domains within different species and remain poorly understood. In the present study, we confirmed three conserved VG domains-LPD_N, DUF1943, and VWD-in the Chinese mitten crab (Eriocheir sinensis), highlighting functional similarities of Vg in vertebrates and invertebrates. Of these three domains, DUF1943 and VWD showed definitive bacterial binding activity via interaction with the signature components on microbial surfaces, but this activity was not exhibited by the LPD_N domain. Antibacterial assays indicated that only the VWD domain inhibits bacterial proliferation, and this function may be conserved between different species due to the conserved amino acid residues. To further explore the relationship between Vg and polymeric immunoglobulin receptor (pIgR), we expressed EspIgR and the three E. sinensis Vg (EsVg) domains in HEK293T cells, and coimmunoprecipitation assay demonstrated that only the DUF1943 domain interacts with EspIgR. Subsequent experiments demonstrated that EsVg regulates hemocyte phagocytosis by binding with EspIgR through the DUF1943 domain, thus promoting bacterial clearance and protecting the host from bacterial infection. To the best of our knowledge, our work is the first to report distinct domains in Vg inducing different immunological outcomes in invertebrates, providing new evidence that pIgR acts as a phagocytic receptor for Vg.

Keywords: bacterial infection; hemocyte; invertebrate immunology; phagocytosis; polymeric immunoglobulin receptor (pIgR); vitellogenin (Vg).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacteria / immunology
  • Bacterial Adhesion
  • Base Sequence
  • Crustacea / immunology*
  • HEK293 Cells
  • Hemocytes / immunology
  • Humans
  • Phagocytosis
  • Phylogeny
  • Protein Domains
  • Vitellogenins / chemistry
  • Vitellogenins / metabolism*
  • Vitellogenins / physiology


  • Vitellogenins