Differences in the regulation of microtubule dynamics by microtubule-associated proteins MAP1B and MAP2.

A Vandecandelaere, B Pedrotti, M A Utton, R A Calvert, P M Bayley
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引用次数: 54

Abstract

The regulation of microtubule dynamics in vitro by microtubule-associated proteins (MAPs) was examined, using purified porcine MAP1B and MAP2. MAP1B has a significantly smaller effect on the observed critical concentration for microtubule assembly than MAP2. Assembly is faster in the presence of either MAP, and the resulting microtubules are shorter, indicating that nucleation is substantially promoted by the MAPs. Both MAPs stabilise the microtubule lattice as observed from podophyllotoxin-induced disassembly, but the effect of MAP1B is weaker than the effect of MAP2. At steady-state of assembly MAP1B still allows microtubule dynamic instability to occur as inferred from microtubule length changes. The comparison of the effects of MAP1B and MAP2 indicates that the reduction of the observed critical concentration is attributable to the reduction of the depolymerisation rate and correlates with the extent of suppression of dynamic instability. Numerical simulations illustrate that microtubule dynamics are strongly influenced by relatively small changes in the strength of a limited subset of subunit interactions in the lattice. The observed characteristic differences between the MAPs may be important for the regulation of distinct populations of microtubules which coexist in the same cell, where differences in stability and dynamics may be essential for their different spatial roles as, for example, in developing neurons.

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微管相关蛋白MAP1B和MAP2对微管动力学调控的差异
利用纯化的猪MAP1B和MAP2,研究了微管相关蛋白(MAPs)对体外微管动力学的调控作用。MAP1B对观察到的微管组装临界浓度的影响明显小于MAP2。在任何一种MAP存在的情况下,微管的组装速度都更快,形成的微管也更短,这表明MAP极大地促进了微管的成核。从鬼臼毒素诱导的分解中观察到,这两种map都能稳定微管晶格,但MAP1B的作用弱于MAP2。在装配稳态时,MAP1B仍然允许微管发生动态不稳定性,这是由微管长度变化推断出来的。对MAP1B和MAP2作用的比较表明,观察到的临界浓度的降低是由于解聚合速率的降低,并且与抑制动态不稳定性的程度有关。数值模拟表明,微管动力学受到晶格中有限亚基相互作用强度的相对较小变化的强烈影响。观察到的map之间的特征差异可能对同一细胞中共存的不同微管群体的调节很重要,其中稳定性和动力学的差异可能对其不同的空间作用至关重要,例如,在发育神经元中。
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