微管趋化模型

D.J. Oddel
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引用次数: 0

摘要

微管(MT)细胞骨架的戏剧性重组是包括有丝分裂和轴突起始在内的许多细胞过程的基础。体内的MT组装由MT组装调节剂调节,而MT组装调节剂本身通常由拮抗的激酶/磷酸酶对调节,这样磷酸化的形式是活跃的,而去磷酸化的形式是不活跃的。如果拮抗活性在细胞中是空间分离的,那么应该存在一个稳定的梯度来有效地促进MT在一个区域的组装和/或抑制另一个区域的组装。这一机制被用来解释mt在有丝分裂期间是如何被募集到染色体上的。目前尚不清楚的是,在什么条件下这种梯度可以预期存在于细胞中。为了定量预测这种梯度,开发了激酶/磷酸酶反应的反应-扩散模型。利用典型的反应速率常数和扩散系数,预测在10 /spl mu/m距离内,浓度变化将达到10倍。这样的梯度预计会对MT组装动力学产生重大影响,有效地将微管招募到细胞的特定亚区。这种招募机制与细菌趋化性相似,所以我称之为“微管趋化”。
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Model for microtubule chemotaxis
Dramatic reorganization of the microtubule (MT) cytoskeleton underlies a number of cellular processes including mitosis and axon initiation. MT assembly in vivo is regulated by MT assembly modulators, which are themselves regulated, often by antagonistic kinase/phosphatase pairs such that the phosphorylated form is active while the dephosphorylated form is inactive. If the antagonistic activities are spatially segregated in the cell, then a stable gradient should exist to effectively promote MT assembly in one region and/or inhibit assembly in another region. This mechanism has been invoked to explain how MTs are recruited to chromosomes during mitosis. What is not known is under what conditions such gradients can be expected to exist in the cell. To quantitatively predict such gradients, a reaction-diffusion model of the kinase/phosphatase reactions was developed. Using typical reaction rate constants and diffusion coefficients, it was predicted that a 10-fold concentration change should exist over a 10 /spl mu/m distance. Such a gradient would be expected to exert a substantial Influence over MT assembly dynamics, effectively recruiting microtubules to a particular subregion of the cell. The recruitment mechanism is reminiscent of and analogous to bacterial chemotaxis, so I call it "microtubule chemotaxis".
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