Deceivingly dynamic: Learning-dependent changes in stathmin and microtubules.
Deceivingly dynamic: Learning-dependent changes in stathmin and microtubules.
复制标题
令人难以置信的动态：stathmin 和微管的学习依赖性变化。
DOI：
10.1016/j.nlm.2015.07.011
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发表时间：
2015
影响因子：
2.7
通讯作者：
Shumyatsky,GlebP
中科院分区：
文献类型：
--
作者：
Uchida,Shusaku;Shumyatsky,GlebP
微管是主要的细胞骨架结构之一，以前被认为是稳定的，只间接参与成熟神经元的突触结构和功能。然而，最近的证据表明，微管是动态的，在突触结构、突触可塑性和记忆中发挥着重要作用。特别是，学习导致微管更新和稳定性的变化，药物对微管动力学的操纵改变了突触的可塑性和长期记忆。这些学习诱导的微管变化由磷酸蛋白stathmin控制，其唯一已知的细胞活动是负向调节微管的形成。在学习后的头8小时内，stathmin的磷酸化变化经历了两个阶段，导致微管稳定性/不稳定性的双相变化。这些转变反过来通过在第二阶段控制AMPA受体的GluA2亚单位的突触运输来调节记忆的形成。在老年动物以及阿尔茨海默病和抑郁症患者中，已经观察到stathmin和微管动力学的不正确调节。因此，最近对stathmin和微管的研究已经在记忆编码的早期阶段发现了新的分子参与者。
Microtubules, one of the major cytoskeletal structures, were previously considered stable and only indirectly involved in synaptic structure and function in mature neurons. However, recent evidence demonstrates that microtubules are dynamic and have an important role in synaptic structure, synaptic plasticity, and memory. In particular, learning induces changes in microtubule turnover and stability, and pharmacological manipulation of microtubule dynamics alters synaptic plasticity and long-term memory. These learning-induced changes in microtubules are controlled by the phosphoprotein stathmin, whose only known cellular activity is to negatively regulate microtubule formation. During the first eight hours following learning, changes in the phosphorylation of stathmin go through two phases causing biphasic shifts in microtubules stability/instability. These shifts, in turn, regulate memory formation by controlling in the second phase synaptic transport of the GluA2 subunit of AMPA receptors. Improper regulation of stathmin and microtubule dynamics has been observed in aged animals and in patients with Alzheimer’s disease and depression. Thus, recent work on stathmin and microtubules has identified new molecular players in the early stages of memory encoding.