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Published on: January 22, 2019
β-Arrestin 1's Interaction with TC45 Attenuates Stat signaling by dephosphorylating Stat to inhibit antimicrobial
Jie-Jie Sun1, Hui-Ting Yang1, Guo-Juan Niu1
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, 250100, China.
Abstract:
Impaired phosphatase activity leads to the persistent activation of signal transducers and activators of transcription (Stat). In mammals, Stat family members are often phosphorylated or dephosphorylated by the same enzymes. To date, only one Stat similar to mammalian Stat5a/b has been found in crustaceans and there have been few studies in Stat signal regulation in crustaceans. Here, we report that β-arrestin1 interacts with TC45 (45-kDa form of T cell protein tyrosine phosphatase) in the nucleus to attenuate Stat signaling by promoting dephosphorylation of Stat. Initially, we showed that Stat translocates into the nucleus to induce antimicrobial peptide (AMP) expression after bacterial infection. βArr1 enters the nucleus of hemocytes and recruits TC45 to form the βarr1-TC45-Stat complex, which dephosphorylates Stat efficiently. The interaction of TC45 with Stat decreased and Stat phosphorylation increased in βarr1-silenced shrimp (Marsupenaeus japonicus) after challenge with Vibrio anguillarum. βArr1 directly interacts with Stat in nucleus and accelerates Stat dephosphorylation by recruiting TC45 after V. anguillarum challenge. Further study showed that βarr1 and TC45 also affect AMP expression, which is regulated by Stat. Therefore, βarr1 and TC45 are involved in the anti-V. anguillarum immune response by regulating Stat activity negatively to decrease AMP expression in shrimp.
Insights
Beta-arrestin1 and TC45 protein tyrosine phosphatase interact in shrimp nuclei to reduce Stat signaling. This interaction dephosphorylates Stat, dampening antimicrobial peptide expression during bacterial infection.
Area of Science:
- Crustacean immunology
- Signal transduction pathways
- Molecular biology
Background:
- Signal transducers and activators of transcription (Stat) signaling is crucial for immune responses.
- Dysregulated Stat activity, often due to impaired phosphatase activity, leads to persistent signaling.
- Stat signal regulation in crustaceans remains understudied.
Purpose of the Study:
- To investigate the role of beta-arrestin1 (βArr1) and TC45 in Stat signal regulation in shrimp.
- To elucidate the mechanism by which βArr1 and TC45 modulate Stat activity during bacterial infection.
Main Methods:
- Studied Stat translocation into the nucleus post-bacterial infection.
- Investigated the interaction of βArr1, TC45, and Stat in shrimp hemocytes.
- Utilized βarr1-silenced shrimp challenged with Vibrio anguillarum to assess Stat phosphorylation and antimicrobial peptide (AMP) expression.
Main Results:
- Stat translocates to the nucleus to induce AMP expression following bacterial infection.
- βArr1 recruits TC45 in the nucleus, forming a complex that dephosphorylates Stat.
- Silencing βArr1 in shrimp led to decreased TC45-Stat interaction and increased Stat phosphorylation after V. anguillarum challenge.
- βArr1 and TC45 negatively regulate Stat activity, thereby decreasing AMP expression.
Conclusions:
- βArr1 and TC45 interact in the nucleus to attenuate Stat signaling by promoting Stat dephosphorylation.
- This βArr1-TC45-Stat complex plays a critical role in the shrimp's anti-Vibrio immune response.
- The findings reveal a novel mechanism of immune regulation in crustaceans involving Stat dephosphorylation.
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