Novel regulation and dynamics of myosin II activation during epidermal wound responses.
Novel regulation and dynamics of myosin II activation during epidermal wound responses.
复制标题
DOI：
10.1016/j.yexcr.2010.01.024
复制
发表时间：
2010-04-01
影响因子：
3.7
通讯作者：
Egelhoff T
中科院分区：
文献类型：
--
作者：
Betapudi V;Rai V;Beach JR;Egelhoff T
皮肤伤口愈合是一个重要而复杂的过程，涉及三维组织重组，包括基质和趋化因子触发的细胞迁移、旁分泌信号传导和基质重塑。在皮肤伤口愈合过程中刺激肌球蛋白 II 活性的分子信号和潜在机制尚未阐明。为了开始了解这一过程中肌球蛋白 II 激活所涉及的信号通路，我们在体外评估了迁移原代人角质形成细胞响应划伤的肌球蛋白 II 激活。我们在此报道，受伤角质形成细胞中肌球蛋白 II 的激活和细胞骨架的募集是双相的。受伤后，肌球蛋白 II 调节轻链 (RLC) 发生快速磷酸化，导致肌球蛋白 IIA 易位至细胞皮层，远远早于随后的极化和细胞迁移。在肌球蛋白 II 激活的急性期，药理学方法揭示 p38-MAP 激酶和胞质钙在驱动细胞骨架组装的磷酸化中具有关键作用。尽管 p38-MAPK 在角质形成细胞迁移中的作用以及在前沿焦点复合体动力学中的作用已知，但据我们所知，这是 p38-MAPK 在任何类型的伤口反应期间充当肌球蛋白 II 磷酸化和组装的上游激活剂的第一份报告。
Wound healing in the skin is an important and complex process that involves 3-dimensional tissue reorganization, including matrix and chemokine-triggered cell migration, paracrine signaling, and matrix remodeling. The molecular signals and underlying mechanisms that stimulate myosin II activity during skin wound healing have not been elucidated. To begin understanding the signaling pathways involved in the activation of myosin II in this process, we have evaluated myosin II activation in migrating primary human keratinocytes in response to scratch wounding in vitro. We report here that myosin II activation and recruitment to the cytoskeleton in wounded keratinocytes is biphasic. Post-wounding, a rapid phosphorylation of myosin II regulatory light chain (RLC) occurs with resultant translocation of myosin IIA to the cell cortex, far in advance of the later polarization and cell migration. During this acute-phase of myosin II activation, pharmacological approaches reveal p38-MAP kinase and cytosolic calcium as having critical roles in the phosphorylation driving cytoskeletal assembly. Although p38-MAPK has known roles in keratinocyte migration, and known roles in leading-edge focal complex dynamics, to our knowledge this is the first report of p38-MAPK acting as an upstream activator of myosin II phosphorylation and assembly during any type of wound response.
登录
查看更多内容
影响因子：
4.4
作者：
Xu, KP;Ding, Y;Yu, FSX
通讯作者：
Yu, FSX
DOI：
10.1083/jcb.200810041
发表时间：
2009-02-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Doyle AD;Wang FW;Matsumoto K;Yamada KM
通讯作者：
Yamada KM
DOI：
10.1016/j.cub.2009.06.044
发表时间：
2009-08-25
期刊：
Current biology : CB
影响因子：
--
作者：
Clark AG;Miller AL;Vaughan E;Yu HY;Penkert R;Bement WM
通讯作者：
Bement WM
影响因子：
4
作者：
Conti, Mary Anne;Adelstein, Robert S.
通讯作者：
Adelstein, Robert S.
影响因子：
11.2
作者：
Betapudi, Venkaiah;Licate, Lucila S.;Egelhoff, Thomas T.
通讯作者：
Egelhoff, Thomas T.