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Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab
Li, Dan1; Wan, Zhicheng1; Li, Xuejie2; Duan, Ming3; Yang, Lei1; Ruan, Zechao1; Wang, Qun1; Li, Weiwei1
Corresponding AuthorWang, Qun(qwang@bio.ecnu.edu.cn) ; Li, Weiwei(wwli@bio.ecnu.edu.cn)
2019-11-01
Source PublicationJOURNAL OF BIOLOGICAL CHEMISTRY
ISSN0021-9258
Volume294Issue:44Pages:16440-16450
AbstractAlternatively-spliced hypervariable immunoglobulin domain-encoding molecules, called Down syndrome cell adhesion molecule (Dscam), have been widely detected as components of the arthropod immune system. Although its ability to specifically bind pathogens and enable phagocytosis of bacteria has been elucidated, the signal transduction mechanisms or effectors that activate post-Dscam?binding pathogens remain poorly characterized. Here, we reveal the alternative splicing exons of Dscam's cytoplasmic tail and its isoforms in the hemocytes of crab (Eriocheir sinensis), showing that the expression of Dscam was acutely induced after an immune challenge, which suggested its functioning for innate immunity. Significantly decreased expression levels of antimicrobial molecular peptides (AMPs) were detected in Dscam-silenced crab hemocytes in vitro, which coincided with their vulnerability to infection by Staphylococcus aureus and higher bacterial concentrations occurring in Dscam-silenced crabs in vivo. Further experimental investigation demonstrated that Dscam-regulated AMP expression via the Src homology (SH)3-binding domain in the first constant exon translated protein of the cytoplasmic tail bound with the SH3 domain of the Dock, an SH3/SH2 adaptor protein required for axon guidance. Dock promoted extracellular signal-regulated kinase (ERK) phosphorylation via indirect binding and then regulated dorsal phosphorylation and translocation from the cytoplasm to the nucleus, subsequently promoting AMP expression for the effective removal of bacteria. To the best of our knowledge, this comprehensive study is the first to highlight the critical role of the alternatively-spliced Dscam cytoplasmic tail in antimicrobial control activity. It also suggests possible cross-talk occurring between Dscam and other pattern recognition receptors.
Keywordinvertebrate bacteria gene transcription toll receptor antimicrobial peptide (AMP) Dock Dscam ERK protein?protein interaction
DOI10.1074/jbc.RA119.010247
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China
Indexed BySCI ; SCI
Language英语
Funding ProjectNational Natural Science Foundation of China[31602189] ; National Natural Science Foundation of China[31672639] ; National Key R&D Program of China[2018YFD0901701] ; National Key R&D Program of China[2018YFD0900605]
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000499478600045
WOS KeywordDROSOPHILA DSCAM ; ADAPTER PROTEIN ; DIVERSITY ; RECEPTOR ; SYSTEM
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Funding OrganizationNational Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China
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Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/34792
Collection淡水生态学研究中心_期刊论文
Corresponding AuthorWang, Qun; Li, Weiwei
Affiliation1.East China Normal Univ, Sch Life Sci, State Key Lab Estuarine & Coastal Res, Lab Invertebrate Immunol Def & Reprod Biol, Shanghai 200241, Peoples R China
2.Dalian Ocean Univ, Coll Fisheries & Life Sci, Dalian 116023, Peoples R China
3.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Li, Dan,Wan, Zhicheng,Li, Xuejie,et al. Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2019,294(44):16440-16450.
APA Li, Dan.,Wan, Zhicheng.,Li, Xuejie.,Duan, Ming.,Yang, Lei.,...&Li, Weiwei.(2019).Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab.JOURNAL OF BIOLOGICAL CHEMISTRY,294(44),16440-16450.
MLA Li, Dan,et al."Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab".JOURNAL OF BIOLOGICAL CHEMISTRY 294.44(2019):16440-16450.
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