Effects of cell tension on the small GTPase Rac.
Effects of cell tension on the small GTPase Rac.
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DOI：
10.1083/jcb.200201105
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发表时间：
2002-07-08
期刊：
影响因子：
--
通讯作者：
Schwartz MA
中科院分区：
文献类型：
--
作者：
Katsumi A;Milanini J;Kiosses WB;del Pozo MA;Kaunas R;Chien S;Hahn KM;Schwartz MA
体内的细胞受到机械应力，例如拉伸、压缩和剪切应力。这些机械应力在生理和病理过程中起着重要的作用，然而，机械应力转换成生化信号的机制仍然是难以捉摸的。在这里，我们表明，等双轴拉伸抑制板状伪足的形成，通过Rac的失活。在10%的菌株中获得了对Rac活性的几乎最大的影响。GAP抗性，组成型活性V12 Rac逆转了这种抑制，支持Rac抑制在响应拉伸中的关键作用。相反，激活内源性Rac与组成型活性核苷酸交换因子没有，这表明GAP活性的调节最有可能介导的抑制。单轴拉伸抑制板状伪足沿着延长拉伸和增加它在相邻的两端。局部化Rac的荧光测定显示单轴拉伸后沿沿着与末端的活性变化相当。通过表达V12 Rac阻断Rac活性的极化阻止了随后的肌动蛋白应力纤维的排列。用抑制肌球蛋白磷酸化和收缩性的Y-27632或ML-7处理通过Rac活化和降低细胞极化增加板状伪足。我们推测，调节Rac活动的紧张可能是重要的运动，极化，和细胞运动的方向性。
Cells in the body are subjected to mechanical stresses such as tension, compression, and shear stress. These mechanical stresses play important roles in both physiological and pathological processes; however, mechanisms transducing mechanical stresses into biochemical signals remain elusive. Here, we demonstrated that equibiaxial stretch inhibited lamellipodia formation through deactivation of Rac. Nearly maximal effects on Rac activity were obtained with 10% strain. GAP-resistant, constitutively active V12Rac reversed this inhibition, supporting a critical role for Rac inhibition in the response to stretch. In contrast, activation of endogenous Rac with a constitutively active nucleotide exchange factor did not, suggesting that regulation of GAP activity most likely mediates the inhibition. Uniaxial stretch suppressed lamellipodia along the sides lengthened by stretch and increased it at the adjacent ends. A fluorescence assay for localized Rac showed comparable changes in activity along the sides versus the ends after uniaxial stretch. Blocking polarization of Rac activity by expressing V12Rac prevented subsequent alignment of actin stress fibers. Treatment with Y-27632 or ML-7 that inhibits myosin phosphorylation and contractility increased lamellipodia through Rac activation and decreased cell polarization. We hypothesize that regulation of Rac activity by tension may be important for motility, polarization, and directionality of cell movement.
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DOI：
10.1083/jcb.102.4.1400
发表时间：
1986-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kolega J
通讯作者：
Kolega J
影响因子：
21.3
作者：
Del Pozo, MA;Kiosses, WB;Schwartz, MA
通讯作者：
Schwartz, MA
影响因子：
21.3
作者：
Balaban, NQ;Schwarz, US;Geiger, B
通讯作者：
Geiger, B
DOI：
10.1083/jcb.153.6.1175
发表时间：
2001-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Riveline D;Zamir E;Balaban NQ;Schwarz US;Ishizaki T;Narumiya S;Kam Z;Geiger B;Bershadsky AD
通讯作者：
Bershadsky AD
影响因子：
3.3
作者：
Cox, EA;Sastry, SK;Huttenlocher, A
通讯作者：
Huttenlocher, A