Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the Brain.
Tale of the Good and the Bad Cdk5: Remodeling of the Actin Cytoskeleton in the Brain.
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DOI：
10.1007/s12035-017-0525-3
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发表时间：
2018-04
影响因子：
5.1
通讯作者：
Rossie S
中科院分区：
文献类型：
--
作者：
Shah K;Rossie S
cdk 5激酶是细胞周期蛋白依赖性激酶家族成员，是脑细胞骨架重塑的关键调节因子。cdk 5在胚胎发育过程中对大脑发育至关重要。出生后，它对许多神经元过程至关重要，如学习和记忆形成，药物成瘾，疼痛信号和长期行为变化，所有这些都依赖于细胞骨架的快速变化。Cdk 5活性在包括阿尔茨海默病、帕金森病、肌萎缩性侧索硬化和缺血性中风的各种脑疾病中失调，导致神经元细胞骨架的深刻重塑、突触的丧失和最终的神经变性。本文综述了Cdk 5在脑内的“好与坏”及其在调节神经元肌动蛋白细胞骨架重塑中的多效性作用。绝大多数生理和病理Cdk 5底物与肌动蛋白细胞骨架相关。因此，我们特别强调的是在过去二十年中鉴定的许多Cdk 5底物，如ephexin 1，p27，Mst 3，CaMKv，kalirin-7，RasGRF 2，Pak 1，WAVE 1，neurabin-1，TrkB，5-HT 6 R，talin，dreplant，synapsin I，synapsin III，CRMP 1，GKAP，SPAR，PSD-95和LRRK 2。这些底物已解开的分子机制，Cdk 5发挥不同的作用，在调节神经元肌动蛋白细胞骨架动力学在健康和患病状态。
Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration. This review focuses on the “good and bad” Cdk5 in the brain and its pleiotropic contribution in regulating neuronal actin cytoskeletal remodeling. A vast majority of physiological and pathological Cdk5 substrates are associated with the actin cytoskeleton. Thus, our special emphasis is on the numerous Cdk5 substrates identified in the past two decades such as ephexin1, p27, Mst3, CaMKv, kalirin-7, RasGRF2, Pak1, WAVE1, neurabin-1, TrkB, 5-HT6R, talin, drebrin, synapsin I, synapsin III, CRMP1, GKAP, SPAR, PSD-95, and LRRK2. These substrates have unraveled the molecular mechanisms by which Cdk5 plays divergent roles in regulating neuronal actin cytoskeletal dynamics both in healthy and diseased states.
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