THE ADF/COFILIN PROTEINS - STIMULUS-RESPONSIVE MODULATORS OF ACTIN DYNAMICS
THE ADF/COFILIN PROTEINS - STIMULUS-RESPONSIVE MODULATORS OF ACTIN DYNAMICS
复制标题
DOI：
10.1091/mbc.6.11.1423
复制
发表时间：
1995-11-01
影响因子：
3.3
通讯作者：
DRUBIN, DG
中科院分区：
文献类型：
--
作者：
MOON, A;DRUBIN, DG
无论细胞是利用肌动蛋白聚合来产生运动，为胞质分裂做准备，还是组装长寿命的基于肌动蛋白的结构，如肌节或微绒毛，肌动蛋白聚合都必须在时间和空间上受到控制。肌动蛋白组织的变化通常发生在一个时间尺度上，该时间尺度决定了信号转导装置与控制肌动蛋白组装的机器的紧密耦合。当运动细胞沿着趋化剂梯度增加的方向延伸伪足时，就是这种情况。为了介导这样的应答，真核细胞配备有一组肌动蛋白结合蛋白（Stossel等人，1985; Pollard和库珀，1986）。几条证据线现在已经汇聚到牵连ADF/cofilin蛋白，特别是作为肌动蛋白动力学的刺激响应介质。ADF/cofilins具有多种调节组装的活性，并且这些活性被体内发生的磷酸化抑制。值得注意的是，ADF/cofilins经历快速去磷酸化时，细胞暴露于刺激，导致细胞骨架组装的变化。ADF/cofilins的作用和活性可受pH、PIP 2、肌动蛋白亲和结合核苷酸的性质和pH值的影响，蛋白质的ADF/Cofilin家族肌动蛋白单体可逆地自结合形成肌动蛋白丝（F-actin），肌动蛋白的唯一功能形式低分子量（15-22 kDa）ADF/cofilin蛋白在体外表现出单体结合、单体结合、单体切断和核苷酸解离抑制活性，表明这些蛋白在细胞中的作用是使微丝不稳定并相应地增加单体肌动蛋白的量。本文就ADF/cofilin蛋白的生物化学研究进展作一综述。
Whether a cell is harnessing actin polymerization to produce movement, preparing for cytokinesis, or as-sembling long-lived actin filament-based structures such as sarcomeres or microvilli, actin polymerization must be controlled in time and space. Changes in actin organization often occur on a timescale that dictates an intimate coupling of a signal transduction apparatus to the machinery that controlsactin assembly. This is the case when a motile cell extends pseudopodia in the direction of a gradient of increasing chemoattrac-tant. To mediate such responses, eukaryotic cells are equipped with a battery of actin-binding proteins (Stossel et al., 1985; Pollard and Cooper, 1986). Several lines of evidence have now converged to implicate the ADF/cofilin proteins in particular as stimulus-respon-sive mediators of actin dynamics. The ADF/cofilins are endowed with multiple activities that can modulate assembly, and these activities are inhibited by a phosphorylation thatoccurs in vivo. Significantly, ADF/cofilins undergo rapid dephosphorylation when cells are exposed to stimuli that cause changes in cytoskeletal assembly. Additional regulatory possibil-ities are suggested by observations that the actions and activities of ADF/cofilins can be influenced by pH, PIP2, the nature of the actin filament-bound nucleotide (ATP or ADP), inorganic phosphate, andpos-sibly, translocationinto the nucleus and tension on the actin filament.THE ADF/COFILIN FAMILY OF PROTEINS Actin monomers reversibly self-associate to form actin filaments (F-actin), the only form of actin known to be functional. The low molecular mass (15-22 kDa) ADF/cofilin proteins exhibit monomer-binding, filament-binding, filament-severing, and nucleotide dissocia-tion-inhibiting activities in vitro, which suggest that the role of these proteins in the cell is to destabilize filaments and correspondingly increase the amount of monomeric actin. In this review, the extensive biochemical studies on the ADF/cofilin proteins are an-