The Mechanism of Intracellular Transport and Kinesin Motors, KIFs : Structure, Function, Dynamics and Regulation

一般而言，细胞内转运是细胞功能的基础。我们重点研究了运动蛋白超家族蛋白(KIFs)的这种作用机制。对13个新的KIF的一级结构进行了求解。利用分子细胞生物学和分子遗传学的方法，我们发现KIF4是决定幼年神经元活性的关键分子，KIF26A通过抑制GDNF/Ret信号而对肠道神经系统的发育起重要作用，KIF17不仅通过转运NDMA受体，而且通过CREB的磷酸化和泛素蛋白酶体依赖的NR2A的降解来控制NR2B和KIF17的转录和翻译。我们解决了Mg^&lt；++&gt；过程中的原子结构和水从Mg^&lt；++&gt；ADP中释放的问题，因此我们解决了ATP水解过程中的几乎所有状态，这为我们理解Kifs如何沿微管运动奠定了坚实的基础。

Intracellular transport is fundamental for cellular functions in cells in general. We studied this mechanism focusing on the kinesin superfamily proteins (KIFs). The primary structures of 13 new KIFs were solved. Using molecular cell biology and molecular genetics we revealed that KIF4 is a key molecule determining activity dependent survival or death of juvenile neurons, that KIF26A is fundamental for development of enteric nervous system by acting as a suppressor for GDNF/Ret signaling, and that KIF17 plays a significant role by not only transporting NDMA receptors, but also controlling transcription and translation of NR2B and KIF17 through CREB phosphorylation and ubiquitin-proteasome dependent degradation of NR2A. We solved atomic structures during Mg^<++> and water release from Mg^<++>ADP so that we solved almost all states during ATP hydrolysis which gives us strong bases to understand how KIFs move along microtubules.