NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization.
NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization.
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DOI：
10.1128/mcb.00424-16
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发表时间：
2017-04-15
影响因子：
5.3
通讯作者：
Kinashi T
中科院分区：
文献类型：
--
作者：
Kondo N;Ueda Y;Kita T;Ozawa M;Tomiyama T;Yasuda K;Lim DS;Kinashi T
免疫突触形成过程中T细胞与抗原提呈细胞（APC）之间的抗原特异性粘附由LFA-1和ICAM-1介导。在这里，LFA-1-ICAM-1的相互作用，在单分子水平上支持的脂质双层测量。在低频率的内周超分子激活簇（SMAC）区，含有高水平的激活Rap 1和kindlin-3的高亲和力结合检测。Rap 1是T细胞附着所必需的，而ste 20样激酶Mst 1/Mst 2的缺陷，减少了高亲和力结合，并废除了中央SMAC（cSMAC）的形成与错误定位的kindlin-3和囊泡转运调节剂参与T细胞受体回收/释放机制，导致T细胞-APC相互作用受损。我们发现，通过RAPL和Mst 1/Mst 2的Rap 1信号级联激活的NDR 1激酶与Kindlin-3相关并将其募集到IS，这是高亲和力LFA-1/ICAM-1结合和cSMAC形成所必需的。我们的研究结果揭示了Rap 1信号通过NDR 1招募kindlin-3和IS组织的关键作用。
Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Here, LFA-1–ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2, diminished high-affinity binding and abrogated central SMAC (cSMAC) formation with mislocalized kindlin-3 and vesicle transport regulators involved in T cell receptor recycling/releasing machineries, resulting in impaired T cell-APC interactions. We found that NDR1 kinase, activated by the Rap1 signaling cascade through RAPL and Mst1/Mst2, associated with and recruited kindlin-3 to the IS, which was required for high-affinity LFA-1/ICAM-1 binding and cSMAC formation. Our findings reveal crucial roles for Rap1 signaling via NDR1 for recruitment of kindlin-3 and IS organization.
影响因子：
3.7
作者：
Borgman KJ;van Zanten TS;Manzo C;Cabezón R;Cambi A;Benítez-Ribas D;Garcia-Parajo MF
通讯作者：
Garcia-Parajo MF