神经元极性建立和轴突导向的分子机制一直是神经发育和疾病中亟待回答的问题，CDK5可极性表达于生长锥，参与轴突的分化和导向等生理过程，并与神经退行性病、损伤等疾病早期的轴突萎缩相关，但具体机制尚需研究。我们应用定量磷酸化蛋白质谱联合生物信息学绘制了生长锥CDK5磷酸化底物图谱，并对其中关键分子锚蛋白B（AnkB）的磷酸化调控轴突分化导向在生理及疾病中的分子机理做深入探讨，希望通过证明：①CDK5可以磷酸化AnkB的S1923和S3819位点；②生理状态：神经元发育中，S1923磷酸化介导AnkB的440-KD剪切异构体在轴突中极性分布，参与轴突分化；成熟神经元中，生长锥局部 S3819磷酸化/脱磷酸化介导细胞骨架网络与细胞膜的锚定和解锚定，参与轴突导向；③病理状态：在帕金森氏病早期CDK5过度磷酸化AnkB参与黑质神经元早期轴突退变；为神经系统发育、疾病的研究提供新的研究思路和药物设计靶点。

Neuronal polarity is the structural basis of neuronal functional. Asymmetric distribution of the axonal proteins was regulated by protein kinases,such as CDK5 etc., but the mechanism is not clear yet. In this project, we used iTRAQ (isobaric tags for relative and absolute quantification) and MS/MS to draw the substrate spectrum of CDK5 phoisphorylation sites in axonal growth cone. Furthermore, we study the molecular mechanism of CDK5-mediated phosphorylation of Ankyrin B in axonal polarity formation and asymmetric distribution in growth cone. We intende to identify the CDK5 phosphorylation sites on Ankyrin B. To test the asymmetric distribution of Ankyrin B in axonal development, and it's relationship with CDK5-mediated phosphorylation. To investigate the correlationship between the binding/unbinding of Actin/spectrin skeleton network and integral membrane protein L1CAM, and CDK5-mediated phosphorylation/dephosphorylation of Ankyrin B. To detect the local asymmetric activation of CDK5 and subsequent phosphorylation of Ankyrin B in grownth cone durin stimulation of axon guidance cues, such as BDNF or Slit. To investigate activation of CDK5/Ankyrin B signalling, and consequtntly, axon collapse and neuronal apoptosis in the mouse substantia nigra neurons in Parkinson's disease models. This study reveals the molecular mechanism of neuronal polarity formation, axons differentiation and axon guidance. And provides theoretical reference for the developing nervous system, and provide a new therapeutical strategy for nerve damage and degenerative diseases.