Tau avoids the GTP cap at growing microtubule plus ends
Tau avoids the GTP cap at growing microtubule plus ends
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Tau 避免生长微管正端的 GTP 帽
DOI：
10.1101/2019.12.31.891234
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
D. Odde
中科院分区：
文献类型：
--
作者：
B. Castle;Kristen McKibben;E. Rhoades;D. Odde
正末端追踪蛋白（+TIPs）是一类与微管生长端相关的蛋白质，介导神经发育和细胞分裂等重要细胞功能。近年来的研究表明，大多数+TIP通过末端结合蛋白（EB）家族定向至正末端，其优先结合微管生长期间存在的GTP-微管蛋白的稳定帽，而与近端微管中的GDP-微管蛋白的结合较弱。一个有待解决的问题是是否可能存在其他微管相关蛋白（MAP），优先结合特定的核苷酸状态的微管蛋白。在这里，我们报告了神经元MAP tau，它富含轴突，在那里它促进微管的生长和捆绑，在体外优先结合GDP-微管蛋白（KD = 0.26 μM）超过GMPCPP-微管蛋白（KD = 1.1 μM），以及在体外和体内生长的微管尖端的GTP-微管蛋白。这种核苷酸偏好性导致tau结合在体外和活细胞中均滞后于生长的微管正末端约100-200 nm。因此，tau蛋白是一种微管尖端回避蛋白，建立了一类新的尖端回避MAP，主要通过抑制微管缩短而不是促进生长来起作用。我们推测，神经系统疾病相关的tau突变可能通过其未能正确识别GDP-微管蛋白而发挥其表型，从而将+TIPs（如EB 3）及其相关活性转移到神经元中的异常位置。
Plus-end tracking proteins (+TIPs) are a group of proteins that associate with the growing end of microtubules and mediate important cellular functions including neural development and cell division. Work in recent years has shown that the majority of +TIPs are directed to the plus-end through a family of end binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth, versus weaker binding to GDP-tubulin in the proximal microtubule. One question yet to be addressed is whether there may exist other microtubule associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here we report that the neuronal MAP tau, which is enriched in axons where it promotes microtubule growth and bundling, preferentially binds GDP-tubulin (KD = 0.26 µM) over GMPCPP-tubulin (KD = 1.1 µM) in vitro as well as GTP-tubulin at the tips of growing microtubules in vitro and in vivo. This nucleotide preference causes tau binding to lag behind the growing microtubule plus-end by about 100-200 nm both in vitro and in live cells. Thus, tau is a microtubule tip avoiding protein, establishing a new class of tip avoiding MAPs, and acts primarily by suppressing microtubule shortening rather than promoting growth. We speculate that neurological disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin, thus displacing +TIPs, such as EB3, and their associated activities into abnormal locations in the neuron.
体内 enconsin 微管结合的快速动力学。
影响因子：
4
作者：
Bulinski,JC;Odde,DJ;Howell,BJ;Salmon,TD;Waterman-Storer,CM
通讯作者：
Waterman-Storer,CM
脑微管相关蛋白在体外调节微管动态不稳定性。
影响因子：
4
作者：
Pryer,NK;Walker,RA;Skeen,VP;Bourns,BD;Soboeiro,MF;Salmon,ED
通讯作者：
Salmon,ED
影响因子：
3.4
作者：
Li, Xiao-Han;Rhoades, Elizabeth
通讯作者：
Rhoades, Elizabeth