Drechsel D N, Hyman A A, Cobb M H, Kirschner M W
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Mol Biol Cell. 1992 Oct;3(10):1141-54. doi: 10.1091/mbc.3.10.1141.
Microtubule-associated proteins (MAP), such as tau, modulate the extent and rate of microtubule assembly and play an essential role in morphogenetic processes, such as axonal growth. We have examined the mechanism by which tau affects microtubule polymerization by examining the kinetics of microtubule assembly and disassembly through direct observation of microtubules using dark-field microscopy. Tau increases the rate of polymerization, decreases the rate of transit into the shrinking phase (catastrophe), and inhibits the rate of depolymerization. Tau strongly suppresses the catastrophe rate, and its ability to do so is independent of its ability to increase the elongation rate. Thus, tau generates a partially stable but still dynamic state in microtubules. This state is perturbed by phosphorylation by MAP2 kinase, which affects all three activities by lowering the affinity of tau for the microtubule lattice.
微管相关蛋白（MAP），如tau蛋白，可调节微管组装的程度和速率，并在形态发生过程（如轴突生长）中发挥重要作用。我们通过暗视野显微镜直接观察微管，研究微管组装和解聚的动力学，从而探究tau蛋白影响微管聚合的机制。tau蛋白可提高聚合速率，降低进入收缩期（灾变）的速率，并抑制解聚速率。tau蛋白强烈抑制灾变率，且其抑制能力与其增加伸长率的能力无关。因此，tau蛋白在微管中产生了一种部分稳定但仍具动态性的状态。这种状态会因MAP2激酶的磷酸化作用而受到干扰，MAP2激酶通过降低tau蛋白对微管晶格的亲和力来影响所有这三种活性。
