Vibrio splendidus flagellin C binds tropomodulin to induce p38 MAPK-mediated p53-dependent coelomocyte apoptosis in Echinodermata.

Autor: Dai F; State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, Ningbo, China; State-Province Joint Laboratory of Marine Biotechnology and Engineering, Ningbo University, Ningbo, China., Guo M; State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, Ningbo, China; State-Province Joint Laboratory of Marine Biotechnology and Engineering, Ningbo University, Ningbo, China., Shao Y; State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, Ningbo, China; State-Province Joint Laboratory of Marine Biotechnology and Engineering, Ningbo University, Ningbo, China., Li C; State Key Laboratory for Quality and Safety of Agro-products, Ningbo University, Ningbo, China; State-Province Joint Laboratory of Marine Biotechnology and Engineering, Ningbo University, Ningbo, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, PR China. Electronic address: lichenghua@nbu.edu.cn.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2022 Jul; Vol. 298 (7), pp. 102091. Date of Electronic Publication: 2022 May 30.
DOI: 10.1016/j.jbc.2022.102091
Abstrakt: As a typical pathogen-associated molecular pattern, bacterial flagellin can bind Toll-like receptor 5 and the intracellular NAIP5 receptor component of the NLRC4 inflammasome to induce immune responses in mammals. However, these flagellin receptors are generally poorly understood in lower animal species. In this study, we found that the isolated flagellum of Vibrio splendidus AJ01 destroyed the integrity of the tissue structure of coelomocytes and promoted apoptosis in the sea cucumber Apostichopus japonicus. To further investigate the molecular mechanism, the novel intracellular LRR domain-containing protein tropomodulin (AjTmod) was identified as a protein that interacts with flagellin C (FliC) with a dissociation constant (K d ) of 0.0086 ± 0.33 μM by microscale thermophoresis assay. We show that knockdown of AjTmod also depressed FliC-induced apoptosis of coelomocytes. Further functional analysis with different inhibitor treatments revealed that the interaction between AjTmod and FliC could specifically activate p38 MAPK, but not JNK or ERK MAP kinases. We demonstrate that the transcription factor p38 is then translocated into the nucleus, where it mediates the expression of p53 to induce coelomocyte apoptosis. Our findings provide the first evidence that intracellular AjTmod serves as a novel receptor of FliC and mediates p53-dependent coelomocyte apoptosis by activating the p38 MAPK signaling pathway in Echinodermata.
Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article. The A. japonicus were commercially cultured animals, and all the experiments were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The study protocol was approved by the Experimental Animal Ethics Committee of Ningbo University, China.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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