Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding.
Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding.
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DOI：
10.1084/jem.186.8.1347
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发表时间：
1997-10-20
影响因子：
15.3
通讯作者：
Hemler, ME
中科院分区：
文献类型：
--
作者：
Yauch, RL;Felsenfeld, DP;Kraeft, SK;Chen, LB;Sheetz, MP;Hemler, ME
以往的研究表明，整合素α链尾对整合素介导的细胞黏附有很强的积极作用。我们现在在这里表明，整合素α4的尾部缺失显著地削弱了细胞的静态黏附，其机制不涉及可溶性血管细胞黏附分子1配体的结合改变。相反，α4胞质结构域的截断导致整合素在细胞表面聚集的严重不足，这是由配体和/或抗体诱导的。此外，单颗粒示踪技术表明，α4尾部缺失也显著降低了α4β1的膜扩散系数。值得注意的是，低剂量的细胞松弛素D部分恢复了α4尾部缺失时细胞黏附的缺陷。综上所述，这些结果表明，α4尾部的缺失暴露了β1的细胞质结构域，导致细胞骨架结合，明显限制了整合素的横向扩散和聚集到簇中，从而导致细胞静态黏附减少。我们的整合素黏附活性是通过受体扩散/聚集(而不是通过改变配体结合亲和力)调节的，这可能与理解β1整合素由内向外的信号机制高度相关。
Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/ or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside–out signaling mechanisms for β1 integrins.
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影响因子：
7.8
作者：
Chan, P Y;Lawrence, M B;Dustin, M L;Ferguson, L M;Golan, D E;Springer, T A
通讯作者：
Springer, T A
影响因子：
4.8
作者：
BAZZONI, G;SHIH, DT;HEMLER, ME
通讯作者：
HEMLER, ME
DOI：
10.3109/15419069509081293
发表时间：
1995-01-01
期刊：
CELL ADHESION AND COMMUNICATION
影响因子：
--
作者：
Lobb, RR;Antognetti, G;Whitty, A
通讯作者：
Whitty, A
影响因子：
56.9
作者：
MIYAMOTO, S;AKIYAMA, SK;YAMADA, KM
通讯作者：
YAMADA, KM
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