PUBLICATION
Identification of ATP synthase α subunit as a new maternal factor capable of protecting zebrafish embryos from bacterial infection
- Authors
- Ni, S., Zhou, Y., Chen, Y., Du, X., Zhang, S.
- ID
- ZDB-PUB-190914-7
- Date
- 2019
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33(11): 12983-13001 (Journal)
- Registered Authors
- Keywords
- Danio rerio, antibacterial activity, depolarization, maternal immunity, permeabilization
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Anti-Bacterial Agents/pharmacology*
- Bacterial Infections/prevention & control*
- Cytoplasm/metabolism
- Embryo, Nonmammalian/microbiology*
- Mitochondrial Proton-Translocating ATPases/chemistry
- Mitochondrial Proton-Translocating ATPases/metabolism*
- Sequence Homology, Amino Acid
- Zebrafish/embryology*
- PubMed
- 31518507 Full text @ FASEB J.
Citation
Ni, S., Zhou, Y., Chen, Y., Du, X., Zhang, S. (2019) Identification of ATP synthase α subunit as a new maternal factor capable of protecting zebrafish embryos from bacterial infection. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 33(11):12983-13001.
Abstract
Previous studies have shown that ATP synthase α subunit (ATP5A1) plays multiple roles, but our understanding of its biologic functions remains poor and incomprehensive. Here, we clearly demonstrated that zebrafish ATP5A1 was a newly characterized lipoteichoic acid (LTA)- and LPS-binding protein abundantly stored in the eggs and embryos of zebrafish. Zebrafish ATP5A1 acted not only as a pattern recognition receptor, capable of identifying LTA and LPS, but also as an effector molecule, capable of inhibiting the growth of both gram-positive and -negative bacteria. ATP5A1 could disrupt the bacterial membranes by a combined action of membrane depolarization and permeabilization. We also found that the N-terminal 65 residues were critical for the antibacterial activity of zebrafish ATP5A1. In particular, we showed that microinjection of exogenous recombinant (r)ATP5A1 into early embryos could promote their resistance against pathogenic Aeromonas hydrophila challenge, and this pathogen-resistant activity was markedly reduced by the coinjection of anti-ATP5A1 antibody or by the knockdown with morpholino for atp5a1 but not by the coinjection of anti-actin antibody. Moreover, each egg/embryo contains a sufficient amount of ATP5A1 in vivo to kill A. hydrophila. Furthermore, the N-terminal 65 residues 1-65 of ATP5A1 α subunit (rA1-65) with in vitro antibacterial activity also promoted the resistance of embryos against A. hydrophila, but the N-terminal 69 residues 66-134 (rA66-134) or C-terminal residues 135-551 (rA135-551) of ATP5A1 α subunit without in vitro antibacterial activity did not. Finally, we showed that the antibacterial activity of the N-terminal 65 residues of ATP5A1 α subunit was conserved throughout animal evolution. Collectively, these results indicate that ATP5A1 is a novel maternal immunocompetent factor that can protect the early embryos of zebrafish from bacterial infection. This work also provides a new viewpoint for understanding the biologic roles of ATP5A1, which is ubiquitously present in animals.-Ni, S., Zhou, Y., Chen, Y., Du, X., Zhang, S. Identification of ATP synthase α subunit as a new maternal factor capable of protecting zebrafish embryos from bacterial infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping