Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing.
Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing.
复制标题
微管稳定性的学习诱导和依赖于稳定的变化对于记忆至关重要，并且在衰老中受到破坏。
DOI：
10.1038/ncomms5389
复制
发表时间：
2014-07-10
影响因子：
16.6
通讯作者：
Shumyatsky, Gleb P.
中科院分区：
文献类型：
--
作者：
Uchida, Shusaku;Martel, Guillaume;Pavlowsky, Alice;Takizawa, Shuichi;Hevi, Charles;Watanabe, Yoshifumi;Kandel, Eric R.;Alarcon, Juan Marcos;Shumyatsky, Gleb P.
微管稳定性的变化调节了许多生物过程，但它们在记忆中的作用尚不清楚。在这里，我们表明，学习导致海马区微管相关网络的双相变化。在早期，stathmin被去磷酸化，通过促进stathmin与微管蛋白的结合来增强其微管破坏稳定的活性，而在晚期，这些过程被逆转，导致微管/KIF5介导的AMPA受体GluA2亚单位在突触位置的定位增加。微管稳定剂紫杉醇分别在早期或晚期应用时减少或增加记忆。Stathmin突变会破坏微管稳定性、GluA2定位、突触可塑性和记忆的变化。衰老野生型小鼠表现出Stathmin水平、微管稳定性和GluA2定位的损害。阻断GluA2内吞可以挽救stathmin突变和衰老野生型小鼠的记忆缺陷。这些发现证明了微管在年轻人和老年人的记忆中所起的作用。
Changes in the stability of microtubules regulate many biological processes, but their role in memory remains unclear. Here we show that learning causes biphasic changes in the microtubule-associated network in the hippocampus. In the early phase, stathmin is dephosphorylated, enhancing its microtubule-destabilizing activity by promoting stathmin-tubulin binding, whereas in the late phase these processes are reversed leading to an increase in microtubule/KIF5-mediated localization of the GluA2 subunit of AMPA receptors at synaptic sites. A microtubule stabilizer paclitaxel decreases or increases memory when applied at the early or late phases, respectively. Stathmin mutations disrupt changes in microtubule stability, GluA2 localization, synaptic plasticity and memory. Aged wild-type mice show impairments in stathmin levels, changes in microtubule stability, and GluA2 localization. Blocking GluA2 endocytosis rescues memory deficits in stathmin mutant and aged wild-type mice. These findings demonstrate a role for microtubules in memory in young adult and aged individuals.
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DOI：
10.1523/jneurosci.4419-10.2010
发表时间：
2010-11-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bibb JA;Mayford MR;Tsien JZ;Alberini CM
通讯作者：
Alberini CM
影响因子：
5.3
作者：
Hu, Xindao;Viesselmann, Chris;Dent, Erik W.
通讯作者：
Dent, Erik W.
影响因子：
4.7
作者：
Hayashi, Kanehiro;Pan, Yong;Bibb, James A.
通讯作者：
Bibb, James A.
DOI：
10.1037/h0077579
发表时间：
1979-01-01
期刊：
JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY
影响因子：
--
作者：
BARNES, CA
通讯作者：
BARNES, CA
影响因子：
56.9
作者：
Brebner, K;Wong, TP;Wang, YT
通讯作者：
Wang, YT