非中心体微管负端蛋白CAMSAPs在神经元极性建立以及迁移的过程中的作用机制研究

微管是细胞骨架的重要组成部分，在神经系统的发育过程中，与神经元的极性建立、迁移、突起的生长与分支及树突棘重塑等过程密不可分。微管的动态及修饰的异常可以直接影响上述过程，并且与神经变性等疾病紧密相关。在神经元中，微管多以非中心体微管的形式存在。CAMSAPs作为非中心体微管负端结合蛋白，在神经元中大量分布，研究表明其与神经元轴突的发育异常以及癫痫等疾病的发生相关，但分子调控机制尚不明了。在前期研究中，我们发现CAMSAP1在神经元的极性建立以及迁移过程中起重要的作用，并且其基因敲除鼠具有抽搐等典型的癫痫特征并致死。因此，深入解析CAMSAP家族蛋白在神经系统发育过程中的调控作用至关重要。本研究以CAMSAP1、2、3基因敲除鼠作为主要研究对象，具体研究它们在神经系统发育过程中的功能，揭示非中心体微管对神经元的极性建立以及迁移的分子调控机制，阐明CAMSAPs在癫痫发病中的作用。

Microtubules are hollow cylindrical filaments assembled form alpha/beta-tubulin heterodimers, the microtubule network is an important component of the cytoskeleton in eukaryotes. Microtubules paly critical roles in fundamental cellular processes such as mitosis, cell motility, intracellular transport and maintenance of cell shape. In many differentiated cells, such as neuron, contain a substantial number of noncentrosomal microtubules. Percent studies have shown that the microtubules play a role in transport, growth cone advancement, neurite extension, branch formation and the remodeling of dendritic spins. Here, the noncentrosomal microtubules minus ends binding proteins, CAMSAPs, also have shown to play a role in axon regeneration and dendrite branching and involved in epilepsy. However, the regulation mechanisms of noncentrosomal microtubules is yet unknown. Now, we have established CAMSAP1, CAMSAP2 and CAMSAP3 conditional knock out mice, to reveal the biologic function of noncentrosomal microtubules further understand the functions of noncentrosomal microtubules in the neuronal developmental process.