Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1.
Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1.
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DOI：
10.4049/jimmunol.0803388
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发表时间：
2009-07-01
期刊：
影响因子：
--
通讯作者：
Kim M
中科院分区：
文献类型：
--
作者：
Hyun YM;Chung HL;McGrath JL;Waugh RE;Kim M
淋巴细胞从血液迁移到淋巴组织或炎症部位是通过细胞表面整合素及其在血管内皮和细胞外基质上表达的配体之间的相互作用发生的。极晚期抗原-4（VLA-4，α4β1）是淋巴细胞有效运输的关键整合素。虽然它已被很好地建立，整合素经历功能上显着的构象变化，介导细胞粘附，有没有机制的信息，解释这些是如何动态和空间调节淋巴细胞极化和迁移。使用动态荧光共振能量转移（FRET）分析的一种新的VLA-4 FRET传感器在全内反射荧光（TIRF）显微镜下，我们表明，VLA-4激活定位于活细胞中的板状伪足。在VCAM-1上的T细胞迁移过程中，VLA-4活化与趋化因子受体的空间重新分布和前缘的活性Rap 1同时发生。用小分子抑制剂在前沿选择性抑制活化的VLA-4足以阻断T细胞迁移。这些数据表明，活化的VLA-4的亚群主要定位于极化的人T细胞的前缘，并且对于VCAM-1上的T细胞迁移至关重要。
Lymphocyte migration from blood into lymphoid tissues or to sites of inflammation occurs through interactions between cell surface integrins and their ligands expressed on the vascular endothelium and the extracellular matrix. Very Late Antigen-4 (VLA-4, α4β1) is a key integrin in the effective trafficking of lymphocytes. Although it has been well established that integrins undergo functionally significant conformational changes to mediate cell adhesion, there is no mechanistic information that explains how these are dynamically and spatially regulated during lymphocyte polarization and migration. Using dynamic fluorescence resonance energy transfer (FRET) analysis of a novel VLA-4 FRET sensor under total internal reflection fluorescence (TIRF) microscopy, we show that VLA-4 activation localizes to the lamellipodium in living cells. During T cell migration on VCAM-1, VLA-4 activation concurs with spatial redistribution of chemokine receptor and active Rap1 at the leading edge. Selective inhibition of the activated VLA-4 at leading edge with a small molecule inhibitor is sufficient to block T cell migration. These data suggest that a subpopulation of activated VLA-4 is mainly localized to the leading edge of polarized human T cells, and is critical for T cell migration on VCAM-1.
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影响因子：
7.3
作者：
Lin, KC;Ateeq, HS;Adams, SP
通讯作者：
Adams, SP
影响因子：
3.4
作者：
Gordon, GW;Berry, G;Herman, B
通讯作者：
Herman, B
影响因子：
56.9
作者：
Kim, M;Carman, CV;Springer, TA
通讯作者：
Springer, TA
影响因子：
20.3
作者：
Chuang, KP;Huang, YF;Shieh, CC
通讯作者：
Shieh, CC
DOI：
10.1083/jcb.200304031
发表时间：
2003-08-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Goldfinger LE;Han J;Kiosses WB;Howe AK;Ginsberg MH
通讯作者：
Ginsberg MH