Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain.
Alpha4beta1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the alpha4-cytoplasmic domain.
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DOI：
10.1083/jcb.200503155
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发表时间：
2005-12-19
期刊：
影响因子：
--
通讯作者：
Ginsberg MH
中科院分区：
文献类型：
--
作者：
Alon R;Feigelson SW;Manevich E;Rose DM;Schmitz J;Overby DR;Winter E;Grabovsky V;Shinder V;Matthews BD;Sokolovsky-Eisenberg M;Ingber DE;Benoit M;Ginsberg MH
整合素介导粘附的能力是由它们的细胞质关联调节的。在这项研究中，我们描述了一种新的机制，通过这种机制α4-整合素的粘附性是由细胞骨架接头帕罗西林调节的。α4尾部突变破坏了paxillin结合，α4(Y991A)，减少了talin与α4β1异源二聚体的结合，破坏了整合素对细胞骨架的锚定，抑制了剪切应力下Jurkat T细胞对VCAM-1的α4β1依赖性捕获和粘附增强。突变体对可溶性或固定的VCAM-1保持固有的亲和性，在短时间接触下支持正常细胞扩散，α - 4微绒毛分布正常，并对内向外信号有响应。这是首次证明整合素的细胞骨架锚定增强了其粘附键在应变下的机械稳定性，从而促进了其在生理剪切应力条件下介导白细胞粘附的能力。
The capacity of integrins to mediate adhesiveness is modulated by their cytoplasmic associations. In this study, we describe a novel mechanism by which α4-integrin adhesiveness is regulated by the cytoskeletal adaptor paxillin. A mutation of the α4 tail that disrupts paxillin binding, α4(Y991A), reduced talin association to the α4β1 heterodimer, impaired integrin anchorage to the cytoskeleton, and suppressed α4β1-dependent capture and adhesion strengthening of Jurkat T cells to VCAM-1 under shear stress. The mutant retained intrinsic avidity to soluble or bead-immobilized VCAM-1, supported normal cell spreading at short-lived contacts, had normal α4-microvillar distribution, and responded to inside-out signals. This is the first demonstration that cytoskeletal anchorage of an integrin enhances the mechanical stability of its adhesive bonds under strain and, thereby, promotes its ability to mediate leukocyte adhesion under physiological shear stress conditions.
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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：
4.8
作者：
Han, JW;Liu, SC;Ginsberg, MH
通讯作者：
Ginsberg, MH
影响因子：
4.8
作者：
Dwir, O;Kansas, GS;Alon, R
通讯作者：
Alon, R
通过L-选择素的细胞质结构域调节白细胞滚动和对高内皮静脉的粘附。
影响因子：
15.3
作者：
Kansas, G S;Ley, K;Munro, J M;Tedder, T F
通讯作者：
Tedder, T F
DOI：
10.1083/jcb.200404160
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim M;Carman CV;Yang W;Salas A;Springer TA
通讯作者：
Springer TA