PDGFRβ Recognizes and Binds Bacteria to Activate Src/Stat Pathway in Oysters
Jiejie Sun1,2, Zhaojun Wu1,2, Wei Wu1,2
1Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.
Abstract:
The Stat signaling pathway plays important roles in mediating the secretions of a large number of cytokines and growth factors in vertebrates, which is generally triggered by the growth factor receptor, cytokine receptor, G protein coupled receptor, and receptor protein tyrosine kinase. In the current study, a platelet-derived growth factor receptor (defined as CgPDGFRβ) was identified from the Pacific oyster Crassostrea gigas, with a signal peptide, three Ig domains, a transmembrane domain, and an intracellular Ser/Thr/Tyr kinase domain. The two N-terminal Ig domains of CgPDGFRβ showed relatively higher binding activity to Gram-negative bacteria and LPS compared with Gram-positive bacteria and peptidoglycan. Upon binding bacteria, CgPDGFRβ in hemocytes formed a dimer and interacted with protein tyrosine kinase CgSrc to induce the phosphorylation of CgSrc at Tyr416. The activated CgSrc interacted with CgStat to induce the translocation of CgStat into the nucleus of hemocytes, which then promoted the expressions of Big defensin 1 (CgBigdef1), IL17-4 (CgIL17-4), and TNF (CgTNF1). These findings together demonstrated that the Src/Stat signaling was activated after the binding of CgPDGFRβ with bacteria to induce the expressions of CgBigdef1, CgIL17-4, and CgTNF1.
Insights
Pacific oyster platelet-derived growth factor receptor (CgPDGFRβ) binds Gram-negative bacteria, activating Src/Stat signaling. This pathway enhances immune responses by promoting the expression of key antimicrobial peptides and cytokines.
Area of Science:
- Marine biology
- Immunology
- Molecular biology
Background:
- The Stat signaling pathway is crucial for cytokine and growth factor secretion in vertebrates.
- This pathway is typically initiated by various cell surface receptors, including growth factor receptors.
Purpose of the Study:
- To identify and characterize a platelet-derived growth factor receptor (PDGFR) in the Pacific oyster, Crassostrea gigas.
- To elucidate the role of CgPDGFRβ in the oyster's immune response to bacterial challenge.
Main Methods:
- Identification and domain analysis of CgPDGFRβ in Crassostrea gigas.
- Bacterial binding assays using Gram-negative and Gram-positive bacteria, and their components (LPS, peptidoglycan).
- Investigation of CgPDGFRβ dimerization, interaction with CgSrc, and subsequent activation of the Src/Stat pathway in hemocytes.
Main Results:
- CgPDGFRβ possesses characteristic domains including Ig domains, a transmembrane domain, and a kinase domain.
- The N-terminal Ig domains of CgPDGFRβ exhibit higher binding affinity for Gram-negative bacteria and LPS.
- Upon bacterial binding, CgPDGFRβ dimerizes, activates CgSrc, leading to CgStat translocation and increased expression of CgBigdef1, CgIL17-4, and CgTNF1.
Conclusions:
- The Src/Stat signaling pathway is activated by CgPDGFRβ in response to bacterial stimuli in oysters.
- This signaling cascade plays a significant role in the innate immune defense of Crassostrea gigas by upregulating antimicrobial and inflammatory gene expression.
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