The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2.
The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2.
复制标题
DOI：
10.1083/jcb.200404160
复制
发表时间：
2004-12-20
期刊：
影响因子：
--
通讯作者：
Springer TA
中科院分区：
文献类型：
--
作者：
Kim M;Carman CV;Yang W;Salas A;Springer TA
整合素β的动态调节是免疫细胞-细胞相互作用和白细胞迁移所必需的。在这里，我们研究细胞粘附和整合素的微簇之间的关系，通过荧光共振能量转移测量，和macroclustering通过高分辨率荧光显微镜测量。通过白细胞功能相关分子-1（LFA-1）激活粘附的刺激未能在配体不存在的情况下改变LFA-1的聚集。单体细胞间粘附分子-1（ICAM-1）的结合诱导了LFA-1构象的深刻变化，但没有改变聚类，而ICAM-1寡聚体的结合诱导了显着的微聚类。增加扩散性的细胞因子破坏剂的膜是足够的亲和力调制的情况下，驱动器的粘附，并与LFA-1的粘附区的更大的积累，但重新分配并不先于细胞粘附。破坏LFA-1细胞外结构域内的构象通讯阻断了由亲和力调节剂刺激的粘附，但不阻断由细胞因子破坏剂刺激的粘附。因此，LFA-1簇不在配体结合之前，而是在与多价配体结合后的粘附增强中起作用。
Dynamic regulation of integrin adhesiveness is required for immune cell–cell interactions and leukocyte migration. Here, we investigate the relationship between cell adhesion and integrin microclustering as measured by fluorescence resonance energy transfer, and macroclustering as measured by high resolution fluorescence microscopy. Stimuli that activate adhesion through leukocyte function–associated molecule-1 (LFA-1) failed to alter clustering of LFA-1 in the absence of ligand. Binding of monomeric intercellular adhesion molecule-1 (ICAM-1) induced profound changes in the conformation of LFA-1 but did not alter clustering, whereas binding of ICAM-1 oligomers induced significant microclustering. Increased diffusivity in the membrane by cytoskeleton-disrupting agents was sufficient to drive adhesion in the absence of affinity modulation and was associated with a greater accumulation of LFA-1 to the zone of adhesion, but redistribution did not precede cell adhesion. Disruption of conformational communication within the extracellular domain of LFA-1 blocked adhesion stimulated by affinity-modulating agents, but not adhesion stimulated by cytoskeleton-disrupting agents. Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands.
登录
查看更多内容
DOI：
10.1083/jcb.153.7.1427
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Laukaitis CM;Webb DJ;Donais K;Horwitz AF
通讯作者：
Horwitz AF
影响因子：
6.4
作者：
Myou, S;Zhu, XD;Leff, AR
通讯作者：
Leff, AR
影响因子：
30.5
作者：
Katagiri, K;Maeda, A;Kinashi, T
通讯作者：
Kinashi, T
影响因子：
56.9
作者：
Kim, M;Carman, CV;Springer, TA
通讯作者：
Springer, TA
DOI：
10.1084/jem.179.4.1307
发表时间：
1994-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Faull RJ;Kovach NL;Harlan JM;Ginsberg MH
通讯作者：
Ginsberg MH