RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1
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DOI：
10.1038/ni950
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发表时间：
2003-08-01
影响因子：
30.5
通讯作者：
Kinashi, T
中科院分区：
文献类型：
--
作者：
Katagiri, K;Maeda, A;Kinashi, T
小的GTdR Rap 1是白细胞整合素的有效激活剂。然而，所涉及的监管机制尚不清楚。在这里，我们确定Rap 1效应器，RAPL，作为一个重要的调节器，在这种激活。RAPL在小鼠淋巴组织中富集，并在T细胞受体和趋化因子CXCL 12刺激后与Rap 1相关。人RAPL刺激淋巴细胞极化和淋巴细胞功能相关抗原1（LFA-1）向前沿的补丁样重新分布，导致与细胞间粘附分子1（ICAM-1）的粘附增强。在Rap 1激活后，RAPL与LFA-1结合，迅速迁移到免疫突触前沿并聚集。因此，RAPL通过LFA-1的空间分布调节淋巴细胞粘附。
The small GTPase Rap1 is a potent activator of leukocyte integrin. However, the regulatory mechanism involved is unknown. Here, we identify the Rap1 effector, RAPL, as an essential regulator in this activation. RAPL was enriched in mouse lymphoid tissues and associated with Rap1 after stimulation by the T cell receptor and with chemokine CXCL12. Human RAPL stimulated lymphocyte polarization and the patch-like redistribution of lymphocyte-function-associated antigen 1 (LFA-1) to the leading edge, resulting in enhanced adhesion to intercellular adhesion molecule 1 (ICAM-1). Triggered by activated Rap1, RAPL associated with LFA-1 and rapidly relocated to the leading edge and accumulated at immunological synapses. Thus, RAPL regulates lymphocyte adhesion through the spatial distribution of LFA-1.