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

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 PKC theta to the membrane, leading to NF-kappa B activation and thus transcription of relevant genes. However, the details of how PKC theta 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 PKC delta activation by interaction with PKC delta, a homologue of PKC theta, which implicates a potential role of ANXA5 involved in PKC theta signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKC theta to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKC theta 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-kappa B signaling in activated T cells. As a result, NF-kappa B 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.