细胞运动中微管网络有序分布的调控机制

细胞运动由信号接收、骨架重排、胞体形变等步骤在时空上精密协调构成。微管是细胞骨架的主要成员，组成动态网络，以保证细胞迁移等诸多功能的顺利实现。在迁移细胞中，微管网络以两种形式存在：在胞体密集分布，在细胞前沿平行排布并指向运动方向。这两种形式不断有序转换，以适应细胞运动方向调整的需求，但其调控机制及功能尚不明了。我们发现，在胞体，微管负端蛋白CAMSAPs定位于微管交叉处，调控微管网络复杂度；在细胞前沿，Nezha/CAMSAP3-ACF7复合体可以协同微丝与微管的逆向流动，为微管平行排布提供动力。以上研究表明CAMSAP家族蛋白质在微管网络的调控中起着重要作用。在本研究中，我们将深入探讨CAMSAP家族蛋白质对微管负端锚定以及微管交叉的调控作用，发掘相关关键蛋白质以及信号转导调控通路，阐明细胞运动中微管网络有序性形成及转换的分子机制和功能，为癌症等疾病治疗提供理论基础。

Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Cell migration requires the coordination of a variety of factors such as cell signaling, dynamics of cytoskeleton, turnover of focal adhesions. Microtubules, the major component of the cytoskeleton, form an intricate network maintaining an exquisite cooperation to build the physical basis for cell migration. The microtubules networks are diverse. In the migrating cells, they are distribute in cell body as mesh networks, and extend forward as brush in the front edge of the cell. However, this precise regulation mechanism of the conversion is unknown yet. .In recent studies, we show that in epithelial cells, the non-centrosomal microtubules crosstalk with F-actin though the minus ends, contribute to regulate cell migration. We demonstrate those non-centrosomal microtubules cooperate with actin filaments through retrograde flow to keep their length and orientation perpendicular to the cell edge. In the other hand, we also found that the minus end proteins of the microtubule, CAMSAPs, also localize at the crosslinking sites of the microtubules, suggesting CAMSAPs play an important role in the regulation of the diversity of microtubules. However, little is known about the molecular mechanism underlying their synergism. In future studies, we are going to deepen the current findings and to study the biological functions of conversation mechanisms of microtubules networks in cell migration.