Nascent Integrin Adhesions Form on All Matrix Rigidities after Integrin Activation

Nascent Integrin Adhesions Form on All Matrix Rigidities after Integrin Activation
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DOI:
10.1016/j.devcel.2015.11.001
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发表时间:
2015-12-07
期刊:
影响因子:
11.8
通讯作者:
Sheetz, Michael P.
Sheetz, Michael P.
中科院分区:
生物学1区
文献类型:
--
作者:
Changede, Rishita;Xu, Xiaochun;Sheetz, Michael P.

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整合素粘附响应于配体结合和机械因素而组装和成熟,但分子水平的组织尚不清楚。我们报告说,类似于100纳米簇的类似于50 β 3-活化的整合素形成非常早期的粘附在各种条件下的RGD表面。这些粘连在流体和刚性基材上形成类似,但大多数粘连在刚性基材上是短暂的。没有塔林或肌动蛋白聚合,很少形成早期粘连,但表达的塔林头或杆结构域在塔林耗尽细胞恢复早期粘连形成。talin杆中整联蛋白结合位点的突变减小了簇的大小。我们认为,整合素簇构成普遍的早期粘附,他们是细胞基质粘附的模块化单位。它们需要活化的整合素与细胞质蛋白,特别是talin和肌动蛋白的关联,并且细胞骨架对它们的收缩导致细胞运动和生长的粘附成熟。
Integrin adhesions assemble and mature in response to ligand binding and mechanical factors, but the molecular-level organization is not known. We report that similar to 100-nm clusters of similar to 50 beta 3-activated integrins form very early adhesions under a wide variety of conditions on RGD surfaces. These adhesions form similarly on fluid and rigid substrates, but most adhesions are transient on rigid substrates. Without talin or actin polymerization, few early adhesions form, but expression of either the talin head or rod domain in talin-depleted cells restores early adhesion formation. Mutation of the integrin binding site in the talin rod decreases cluster size. We suggest that the integrin clusters constitute universal early adhesions and that they are the modular units of cell matrix adhesions. They require the association of activated integrins with cytoplasmic proteins, in particular talin and actin, and cytoskeletal contraction on them causes adhesion maturation for cell motility and growth.