Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching.
Calcium ions and tyrosine phosphorylation interact coordinately with actin to regulate cytoprotective responses to stretching.
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钙离子和酪氨酸磷酸化与肌动蛋白协调相互作用，调节对拉伸的细胞保护反应。
DOI：
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发表时间：
1997
影响因子：
4
通讯作者：
Christopher A. Mcculloch
中科院分区：
文献类型：
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作者：
Michael Glogauer;P. D. Arora;G. Yao;I. Sokholov;Jack Ferrier;Christopher A. Mcculloch
肌动蛋白依赖的感觉和反应元件的基质细胞参与机械信号转导知之甚少。为了研究机械转导，我们先前已经描述了胶原-磁珠模型，其中对整合素施加明确的力诱导立即（< 1秒）钙内流。在这份报告中，我们使用的模型，以确定的作用，钙离子和酪氨酸磷酸化的调节力介导的肌动蛋白组装和由此产生的变化，在膜刚度。胶原珠通过粘着斑相关蛋白talin、黏着斑蛋白、α 2-整联蛋白和β-肌动蛋白与细胞结合，表明力的施加是通过细胞骨架元件介导的。当力（2 N/m2）施加到胶原珠，共聚焦显微镜显示了一个显着的垂直延伸的细胞，这是抵消了肌动蛋白介导的收缩。免疫印迹显示，力的应用诱导F-肌动蛋白积累在珠膜复合物，但黏着斑蛋白，talin和α 2-整联蛋白保持不变。原子力显微镜显示，膜刚度增加6倍，在附近的珠已暴露于力。力还诱导包括桩蛋白在内的几种细胞质蛋白的酪氨酸磷酸化。力诱导的肌动蛋白的积累被阻断在细胞加载BAPTA/AM或在细胞预孵育与染料木素，酪氨酸磷酸化的抑制剂。反复施加力逐渐抑制力诱导的钙离子通量的幅度。由于力诱导的肌动蛋白重组依赖于钙离子和酪氨酸磷酸化，以及膜下皮层中丝状肌动蛋白的逐步增加与膜刚度增加和钙离子内流抑制相关，我们认为皮层肌动蛋白调节拉伸激活的阳离子渗透通道活性，并为暴露于重复的长期机械刺激的细胞提供脱敏机制。肌动蛋白的反应可能是细胞保护，因为它抵消了最初的力介导的膜延伸，并可能加强在力传递点的细胞骨架的完整性。
The actin-dependent sensory and response elements of stromal cells that are involved in mechanical signal transduction are poorly understood. To study mechanotransduction we have described previously a collagen-magnetic bead model in which application of well-defined forces to integrins induces an immediate (< 1 second) calcium influx. In this report we used the model to determine the role of calcium ions and tyrosine-phosphorylation in the regulation of force-mediated actin assembly and the resulting change in membrane rigidity. Collagen-beads were bound to cells through the focal adhesion-associated proteins talin, vinculin, alpha 2-integrin and beta-actin, indicating that force application was mediated through cytoskeletal elements. When force (2 N/m2) was applied to collagen beads, confocal microscopy showed a marked vertical extension of the cell which was counteracted by an actin-mediated retraction. Immunoblotting showed that force application induced F-actin accumulation at the bead-membrane complex but vinculin, talin and alpha 2-integrin remained unchanged. Atomic force microscopy showed that membrane rigidity increased 6-fold in the vicinity of beads which had been exposed to force. Force also induced tyrosine phosphorylation of several cytoplasmic proteins including paxillin. The force-induced actin accumulation was blocked in cells loaded with BAPTA/AM or in cells preincubated with genistein, an inhibitor of tyrosine phosphorylation. Repeated force application progressively inhibited the amplitude of force-induced calcium ion flux. As force-induced actin reorganization was dependent on calcium and tyrosine phosphorylation, and as progressive increases of filamentous actin in the submembrane cortex were correlated with increased membrane rigidity and dampened calcium influx, we suggest that cortical actin regulates stretch-activated cation permeable channel activity and provides a desensitization mechanism for cells exposed to repeated long-term mechanical stimuli. The actin response may be cytoprotective since it counteracts the initial force-mediated membrane extension and potentially strengthens cytoskeletal integrity at force-transfer points.
生物系统中的机械转导。
影响因子：
--
作者：
Sachs,F
通讯作者：
Sachs,F
酪氨酸磷酸化参与响应血清或 LPA 刺激的肌动蛋白细胞骨架的重组。
影响因子：
4
作者：
Chrzanowska-Wodnicka,M;Burridge,K
通讯作者：
Burridge,K
Fc 受体介导的巨噬细胞吞噬作用期间，Fc γ 受体、p72syk 和桩蛋白的 γ 亚基的酪氨酸磷酸化。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Greenberg,S;Chang,P;Silverstein,SC
通讯作者：
Silverstein,SC