A focal adhesion protein-based mechanochemical checkpoint regulates cleft progression during branching morphogenesis.
A focal adhesion protein-based mechanochemical checkpoint regulates cleft progression during branching morphogenesis.
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DOI：
10.1002/dvdy.22714
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发表时间：
2011-09
影响因子：
2.5
通讯作者：
Larsen, Melinda
中科院分区：
文献类型：
--
作者：
Daley, William P.;Kohn, Joshua M.;Larsen, Melinda
裂缝的形成是许多器官分支形态发生的初始步骤。我们以前证明，ROCK 1调节非肌肉肌球蛋白II依赖的机械化学检查点，以过渡启动裂缝发展中的下颌下腺。在这里，我们报告说，ROCK介导的整合素激活和随后形成的粘着斑复合物包括这个机械化学检查点。ROCK 1和非肌肉肌球蛋白II活性的抑制降低了裂隙区整合素β1的活化，并干扰了粘着斑复合物蛋白（如粘着斑激酶（FAK））的定位和活化。FAK活性的抑制也阻止了裂缝的进展，破坏募集的粘着斑蛋白talin和黏着斑蛋白和随后的纤连蛋白组装在裂缝区域，同时减少ERK 1/2激活。这些结果表明，由内而外的整合素信号传导导致活性FAK-含有粘着斑蛋白复合物的局部募集，产生促进分支形态发生进展的机械化学检查点。
Cleft formation is the initial step of branching morphogenesis in many organs. We previously demonstrated that ROCK 1 regulates a non-muscle myosin II-dependent mechanochemical checkpoint to transition initiated clefts to progressing clefts in developing submandibular salivary glands. Here, we report that ROCK-mediated integrin activation and subsequent formation of focal adhesion complexes comprise this mechanochemical checkpoint. Inhibition of ROCK1 and non-muscle myosin II activity decreased integrin β1 activation in the cleft region and interfered with localization and activation of focal adhesion complex proteins, such as focal adhesion kinase (FAK). Inhibition of FAK activity also prevented cleft progression, by disrupting recruitment of the focal adhesion proteins talin and vinculin and subsequent fibronectin assembly in the cleft region while decreasing ERK1/2 activation. These results demonstrate that inside-out integrin signaling leading to a localized recruitment of active FAK-containing focal adhesion protein complexes generates a mechanochemical checkpoint that facilitates progression of branching morphogenesis.
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影响因子：
2.7
作者：
Daley, William P.;Gulfo, Kathryn M.;Sequeira, Sharon J.;Larsen, Melinda
通讯作者：
Larsen, Melinda
影响因子：
4.8
作者：
BAZZONI, G;SHIH, DT;HEMLER, ME
通讯作者：
HEMLER, ME
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
4
作者：
Ballestrem, C;Erez, N;Geiger, B
通讯作者：
Geiger, B
DOI：
10.1083/jcb.200204153
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Galbraith CG;Yamada KM;Sheetz MP
通讯作者：
Sheetz MP