Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow.
Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow.
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DOI：
10.1083/jcb.200301133
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发表时间：
2003-04-28
期刊：
影响因子：
--
通讯作者：
Kinashi T
中科院分区：
文献类型：
--
作者：
Shimonaka M;Katagiri K;Nakayama T;Fujita N;Tsuruo T;Yoshie O;Kinashi T
趋化因子通过快速上调白细胞整合素的黏附活性，阻止血管内的循环淋巴细胞，促进随后的淋巴细胞迁移。然而，调控这一过程的关键调控分子仍然难以捉摸。在这里，我们证明了Rap1在趋化因子诱导的整合素激活和迁移中起着关键作用。次级淋巴组织趋化因子(SLC；CCL21)和基质衍生因子1(CXCL4)在数秒内激活淋巴细胞中的Rap1。RAP1特异性GTP酶激活蛋白Spa1对RAP1的抑制作用、去趋化因子刺激的淋巴细胞通过细胞间黏附分子1在FLOW状态下与内皮细胞快速黏附1.淋巴细胞表达优势活性的RAP1V12刺激抗剪切黏附，细胞在固定化细胞间黏附分子1和血管细胞黏附分子1上的强劲迁移，以及在FLOW状态下的跨内皮细胞黏附。我们还证明了Rap1V12在淋巴细胞中的表达诱导了极化的形态，伴随着CXCR4和CD44分别重新分布到前缘和尾足。SLC处理后，Spa1有效地抑制了这种极化。RAP1的这一独特特性可能控制趋化因子诱导的淋巴细胞外渗。
Chemokines arrest circulating lymphocytes within the vasculature through the rapid up-regulation of leukocyte integrin adhesive activity, promoting subsequent lymphocyte transmigration. However, the key regulatory molecules regulating this process have remained elusive. Here, we demonstrate that Rap1 plays a pivotal role in chemokine-induced integrin activation and migration. Rap1 was activated by secondary lymphoid tissue chemokine (SLC; CCL21) and stromal-derived factor 1 (CXCL4) treatment in lymphocytes within seconds. Inhibition of Rap1 by Spa1, a Rap1-specific GTPase-activating protein, abrogated chemokine-stimulated lymphocyte rapid adhesion to endothelial cells under flow via intercellular adhesion molecule 1. Expression of a dominant active Rap1V12 in lymphocytes stimulated shear-resistant adhesion, robust cell migration on immobilized intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, and transendothelial migration under flow. We also demonstrated that Rap1V12 expression in lymphocytes induced a polarized morphology, accompanied by the redistribution of CXCR4 and CD44 to the leading edge and uropod, respectively. Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation.
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影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
Picker, LJ
DOI：
10.1083/jcb.148.6.1151
发表时间：
2000-03-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Reedquist KA;Ross E;Koop EA;Wolthuis RM;Zwartkruis FJ;van Kooyk Y;Salmon M;Buckley CD;Bos JL
通讯作者：
Bos JL
影响因子：
30.5
作者：
Ostermann, G;Weber, KSC;Weber, C
通讯作者：
Weber, C
影响因子：
56.9
作者：
Laudanna, C;Campbell, JJ;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
56.9
作者：
Li, Z;Jiang, HP;Wu, DQ
通讯作者：
Wu, DQ