Myosin II activation promotes neurite retraction during the action of Rho and Rho-kinase
Myosin II activation promotes neurite retraction during the action of Rho and Rho-kinase
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DOI：
10.1046/j.1365-2443.1998.00181.x
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发表时间：
1998-03-01
期刊：
影响因子：
2.1
通讯作者：
Kaibuchi, K
中科院分区：
文献类型：
--
作者：
Amano, M;Chihara, K;Kaibuchi, K
背景资料：Rho小GTdR通过激活Rho激酶（Rho的靶点）磷酸化肌球蛋白轻链（MLC）来调节肌球蛋白II活性。几条线的证据点的一个重要作用，Rho的溶血磷脂酸（LPA）和凝血酶的行动中挑起神经突起回缩在N1 E-115 neuroblastoma cells.Results：在这里，我们研究了Rho激酶和肌球蛋白II是否参与N1 E-115细胞的神经突起回缩。我们发现，组成型活性形式的Rho激酶的表达诱导N1 E-115细胞中的神经突起收缩和NIH 3 T3细胞中的MLC磷酸化，而显性阴性形式的Rho激酶的表达抑制LPA诱导的N1 E-115细胞中的神经突起收缩和血清诱导的NM 3 T3细胞中的MLC磷酸化。突变体MLCT 18 D、S19 D的表达（用Asp取代Thr和Ser），这是已知的，导致肌球蛋白ATP酶的激活和肌球蛋白II的构象变化，当与肌球蛋白重链在体外重建时，也促进神经突收缩。这些结果表明Rho激酶参与了Rho下游LPA诱导的神经突收缩，肌球蛋白II的激活促进Rho和Rho激酶下游的神经突收缩。
Background: The Rho small GTPase regulates myosin II activity through the phosphorylation of the myosin light chain (MLC) by activating Rho-kinase, which is a target of Rho. Several Lines of evidence point to an important role of Rho in the action of lysophosphatidic acid (LPA) and thrombin in provoking neurite retraction in N1E-115 neuroblastoma cells.Results: Here we examined whether Rho-kinase and myosin II are involved in neurite retraction in N1E-115 cells. We showed that the expression of constitutively active forms of Rho-kinase induced neurite retraction in N1E-115 cells and MLC phosphorylation in NIH 3T3 cells, whereas the expression of dominant negative forms of Rho-kinase inhibited the LPA-induced neurite retraction in N1E-115 cells and the serum-induced MLC phosphorylation in NM 3T3 cells. The expression of mutant MLCT18D,S19D (substitution of Thr and Ser by Asp), which is known to lead to the activation of myosin ATPase and a conformational change of myosin II when reconstituted with myosin heavy chains in vitro, also promoted neurite retraction.Conclusion: These results indicate that Rho-kinase is involved in the LPA-induced neurite retraction downstream of Rho, and that myosin II activation promotes neurite retraction downstream of Rho and Rho-kinase.