期刊
JOURNAL OF CELL SCIENCE
卷 134, 期 16, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258602
关键词
SLP-76; T cell signaling; Immune synapse; Integrin; Microclusters; Myosin
类别
资金
- Brain and Immuno-Imaging Award from the Dana Foundation
- American Heart Association [0635546 T]
- National Institutes of Health [NIH R01 AI07657501, R21-AG030931, T32 AI007077, P30 NS047243, T32 GM008448]
Integrin engagement enhances T cell activation within the immune synapse. Myosin filaments surround and co-transport with SLP76 microclusters, with TCR ligand density governing their movement. Integrin beta 2, kindlin-3 and zyxin are required for complete centripetal transport, with LFA-1 and kindlin-3 having ligand-independent roles.
Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. We show that contractilemyosin filaments surround and are co-transported with SLP76 microclusters, and that TCR ligand density governs the centripetal movement of both structures. Centripetal transport requires formin activity, actomyosin contraction, microtubule integrity and dynein motor function. Although immobilized VLA-4 (alpha 4 beta 1 integrin) and LFA-1 (alpha L beta 2 integrin) ligands arrest the centripetal movement of SLP-76 microclusters and myosin filaments, VLA-4 acts distally, while LFA-1 acts in the lamellum. Integrin beta 2, kindlin-3 and zyxin are required for complete centripetal transport, while integrin beta 1 and talin-1 are not. CD69 upregulation is similarly dependent on integrin beta 2, kindlin-3 and zyxin, but not talin-1. These findings highlight the integration of cytoskeletal systems within the immune synapse and reveal extracellular ligand-independent roles for LFA-1 and kindlin-3.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据