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Annexin A5 is essential for PKCθ translocation during T-cell activation.

ABSTRACT: T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been reported to mediate PKCδ activation by interaction with PKCδ, a homologue of PKCθ, which implicates a potential role of ANXA5 involved in PKCθ signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKCθ to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKCθ upon TCR engagement and blocked the recruitment of CARMA1-BCL10-MALT1 signalosome, which provides a platform for the catalytic activation of IKKs and subsequent activation of canonical NF-κB signaling in activated T cells. As a result, NF-κB activation was impaired in ANXA5-KO T cells. T-cell activation was also suppressed by ANAX5 knockdown in primary T cells. These results demonstrated a novel role of ANXA5 in PKC translocation and PKC signaling during T-cell activation.

SUBMITTER: Hu Z

PROVIDER: S-EPMC7549025 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Annexin A5 is essential for PKCθ translocation during T-cell activation.

Hu Zhaoqing Z Li Lin L Zhu Banghui B Huang Yi Y Wang Xinran X Lin Xiaolei X Li Maoxia M Xu Peipei P Zhang Xuerui X Zhang Jing J Hua Zichun Z

The Journal of biological chemistry 20200812 41

T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been r ...[more]

PMID: 32796034

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Project description:Annexin A5 (ANXA5), which is known as a protein with anticoagulative function, may play a role in triglyceride biosynthesis. Triglycerides are involved in lipid and energy metabolism, which are important in the elucidation of obesity. To investigate the association between single-nucleotide polymorphisms (SNPs) of ANXA5 and obesity in a Korean population, 372 participants (213 overweight/obese individuals and 159 control subjects) were enrolled from the Kyung Hee University Medical Center and Keimyung University Dongsan Medical Center. The genotypes of five SNPs (rs12510548, rs4240260, rs3756281, rs13136094 and rs6534313) were evaluated in ANXA5 using the multiple logistic regression analysis with the codominant 1, codominant 2, dominant, recessive and log-additive models. The genotype and allele frequencies of the five investigated SNPs exhibited significant differences between the control and the overweight/obese groups: rs12510548 (P=0.004 in the codominant 2 model, P=0.0019 in the recessive model, P=0.027 in the log-additive model and P=0.026 in allele frequencies); rs4240260 (P=0.002 and Fisher's exact P=0.0006 in the codominant 2 model, P=0.0007 and Fisher's exact P=0.0007 in the recessive model, P=0.020 and Fisher's exact P=0.0019 in the log-additive model and P=0.020 in allele frequencies); rs3756281 (P=0.016 in the codominant 2 model and P=0.0094 in the recessive model); rs13136094 (P=0.0030 and Fisher's exact P=0.0011 in the codominant 2 model, P=0.0012 and Fisher's exact P=0.0013 in the recessive model, P=0.034 and Fisher's exact P=0.0035 in the log-additive model and P=0.024 in allele frequencies); and rs6534313 (P=0.0010 and Fisher's exact P=0.0003 in the codominant 2 model, P=0.0003 and Fisher's exact P=0.0003 in the recessive model, P=0.0075 and Fisher's exact P=0.0010 in the log-additive model and P=0.005 in allele frequencies). Two haplotypes were weakly associated with obesity (GGATG, P=0.037 and CAGCC, P=0.020). Results of the present study suggested that ANXA5 may be associated with the development of obesity in a Korean population.

Dataset Information

Annexin A5 is essential for PKCθ translocation during T-cell activation.

Publications

Annexin A5 is essential for PKCθ translocation during T-cell activation.

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