Cyclin-Dependent Kinase 5 Links Extracellular Cues to Actin Cytoskeleton During Dendritic Spine Development
Cyclin-Dependent Kinase 5 Links Extracellular Cues to Actin Cytoskeleton During Dendritic Spine Development
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DOI：
10.4161/cam.1.2.4617
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Ip, Nancy Y.
中科院分区：
文献类型：
--
作者：
Fu, Amy K. Y.;Ip, Nancy Y.
新的证据表明，细胞周期蛋白依赖性激酶5(CDK5)在突触可塑性以及高级大脑功能(如学习和记忆)中具有调节作用。然而，CDK5在突触中作用的分子和细胞机制尚不清楚。最近的发现表明，CDK5通过调节肌动蛋白的动力学来调节树突棘的形态发生。Ephexin1和Wave-1是肌动蛋白细胞骨架的两个重要调节因子，最近都被确定为CDK5的底物。重要的是，这些蛋白被CDK5磷酸化导致树突棘丢失，揭示了CDK5调节突触重塑的潜在机制。此外，依赖于CDK5的Ephexin1的磷酸化是ePhin-A1介导的脊椎收缩所必需的，这表明CDK5在将信号从细胞外信号传递到突触处的肌动蛋白细胞骨架中起着关键作用。综上所述，了解CDK5及其下游靶点在突触的精确调控将为了解CDK5在树突棘发育过程中肌动蛋白重塑中的多种调控作用提供重要的见解。
Emerging evidence has indicated a regulatory role of cyclin-dependent kinase 5 (Cdk5) in synaptic plasticity as well as in higher brain functions, such as learning and memory. However, the molecular and cellular mechanisms underlying the actions of Cdk5 at synapses remain unclear. Recent findings demonstrate that Cdk5 regulates dendritic spine morphogenesis through modulating actin dynamics. Ephexin1 and WAVE-1, two important regulators of the actin cytoskeleton, have both been recently identified as substrates for Cdk5. Importantly, phosphorylation of these proteins by Cdk5 leads to dendritic spine loss, revealing a potential mechanism by which Cdk5 regulates synapse remodeling. Furthermore, Cdk5-dependent phosphorylation of ephexin1 is required for the ephrin-A1 mediated spine retraction, pointing to a critical role of Cdk5 in conveying signals from extracellular cues to actin cytoskeleton at synapses. Taken together, understanding the precise regulation of Cdk5 and its downstream targets at synapses would provide important insights into the multi-regulatory roles of Cdk5 in actin remodeling during dendritic spine development.