Actin cytoskeletal dynamics in smooth muscle contraction
Actin cytoskeletal dynamics in smooth muscle contraction
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DOI：
10.1139/y05-088
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发表时间：
2005-10-01
影响因子：
2.1
通讯作者：
Gerthoffer, WT
中科院分区：
文献类型：
--
作者：
Gerthoffer, WT
平滑肌在非常宽的细胞长度范围内产生等长力。这种现象的分子机制尚不清楚，但被描述为反映了平滑肌细胞的“机械可塑性”。可塑性在这里定义为细胞结构或功能响应环境变化而发生的持续变化。触发肌肉可塑性的重要环境刺激包括化学信号（例如神经递质、自体激素和细胞因子）和外部机械信号（例如施加的压力和应变）。这两种信号可能都是通过离子和蛋白激酶信号级联转导来改变基因表达模式以及细胞骨架和收缩系统的变化。定义介导平滑肌表型和机械可塑性的信号机制和效应蛋白是肌细胞生物学的主要目标。一些可能很重要的信号级联包括钙依赖性蛋白激酶、小 GTP 酶（Rho、Rac、cdc42）、Rho 激酶、蛋白激酶 C (PKC)、Src 家族酪氨酸激酶、丝裂原激活蛋白 (MAP) 激酶和 p21 激活蛋白激酶 (PAK)。这些信号级联有许多潜在的靶标，包括核过程、代谢途径和细胞骨架的结构成分。人们越来越认识到平滑肌中肌动蛋白细胞骨架的动态性质以及收缩过程中发生肌动蛋白重塑的必要性。肌动蛋白细胞骨架具有许多可能对肌肉可塑性至关重要的功能，包括力矢量的生成和传递、细胞形状的确定以及信号转导机制的组装。有证据表明肌动蛋白丝是动态的，并且包含收缩元件和肌动蛋白附着位点的肌动蛋白相关蛋白是平滑肌收缩所必需的。
Smooth muscles develop isometric force over a very wide range of cell lengths. The molecular mechanisms of this phenomenon are undefined, but are described as reflecting "mechanical plasticity" of smooth muscle cells. Plasticity is defined here as a persistent change in cell structure or function in response to a change in the environment. Important environmental stimuli that trigger muscle plasticity include chemical (e.g., neurotransmitters, autacoids, and cytokines) and external mechanical signals (e.g., applied stress and strain). Both kinds of signals are probably transduced by ionic and protein kinase signaling cascades to alter gene expression patterns and changes in the cytoskeleton and contractile system. Defining the signaling mechanisms and effector proteins mediating phenotypic and mechanical plasticity of smooth muscles is a major goal in muscle cell biology. Some of the signaling cascades likely to be important include calcium-dependent protein kinases, small GTPases (Rho, Rac, cdc42), Rho kinase, protein kinase C (PKC), Src family tyrosine kinases, mitogen-activated protein (MAP) kinases, and p21 activated protein kinases (PAK). There are many potential targets for these signaling cascades including nuclear processes, metabolic pathways, and structural components of the cytoskeleton. There is growing appreciation of the dynamic nature of the actin cytoskeleton in smooth muscles and the necessity for actin remodeling to occur during contraction. The actin cytoskeleton serves many functions that are probably critical for muscle plasticity including generation and transmission of force vectors, determination of cell shape, and assembly of signal transduction machinery. Evidence is presented showing that actin filaments are dynamic and that actin-associated proteins comprising the contractile element and actin attachment sites are necessary for smooth muscle contraction.