A non-mitotic role for Eg5 in regulating cilium formation and sonic hedgehog signaling  

有丝分裂驱动蛋白Eg5的非经典功能:调节纤毛组装和Shh信号通路

作　　者：Jie Ran Haixia Li Yao Zhang Fan Yu Yunfan Yang Chao Nie Song Yang Dengwen Li Jun Zhou Min Liu 冉杰;李海霞;张瑶;于凡;杨云帆;聂超;杨松;李登文;周军;刘敏(Institute of Biomedical Sciences,Shandong Provincial Key Laboratory of Animal Resistance Biology,Collaborative Innovation Center of Cell Biology in Universities of Shandong,College of Life Sciences,Shandong Normal University,Jinan 250014,China;State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Nankai University,Tianjin 300071,China)

机构地区：[1]Institute of Biomedical Sciences,Shandong Provincial Key Laboratory of Animal Resistance Biology,Collaborative Innovation Center of Cell Biology in Universities of Shandong,College of Life Sciences,Shandong Normal University,Jinan 250014,China [2]State Key Laboratory of Medicinal Chemical Biology,College of Life Sciences,Nankai University,Tianjin 300071,China

出　　处：《Science Bulletin》2021年第16期1620-1623,M0003,共5页科学通报（英文版）

基　　金：This work was supported by the National Key R&D Program of China(2018YFA0107001);the National Natural Science Foundation of China(31671403 and 31701169).

摘　　要：Cilia are hair-like organelles that protrude from the surface of many types of eukaryotic cells.Each cilium possesses a microtubule-based central core,known as the axoneme,surrounded by the ciliary membrane.Ciliogenesis is a multi-step process that typically involves vesicle transport to the centrosome,maturation of the mother centriole into a basal body,docking of the basal body onto the plasma membrane,and extension of the axoneme from the basal body[1].纤毛是一种突出于细胞表面的特化细胞器,存在于哺乳动物体内绝大多数类型的细胞中.纤毛在环境感知、细胞运动等方面发挥重要作用,其缺陷与多种人类疾病相关.纤毛内组分主要在细胞质中合成,通过驱动蛋白家族成员kinesin-2运输到纤毛顶端,从而促进纤毛组装和稳态维持.但是,驱动蛋白家族其他成员在纤毛中的功能尚不清楚.Eg5又称为kinesin-5或KIF11,通过促进两极纺锤体组装,在有丝分裂过程中发挥作用,因此被广泛认为是一个有丝分裂驱动蛋白.本研究发现Eg5具有独立于有丝分裂的一个新功能—调节纤毛组装和Shh信号通路.Eg5在纤毛组装过程中向中心体/纤毛基体富集,对于纤毛的调节依赖于其作为驱动蛋白的ATP酶活性.此外,Eg5异常引起的纤毛缺陷会阻止Shh刺激下Smo向纤毛膜上的转移,进一步抑制Gli蛋白的激活和下游基因的转录.这些发现促进了对纤毛组装调控机制的认识,并为理解小头畸形、肿瘤等Eg5异常相关人类疾病提供了新思路.

关 键 词：家族其他成员 小头畸形 驱动蛋白 Eg5 有丝分裂 人类疾病 ATP酶活性 环境感知 

分 类 号：Q253[生物学—细胞生物学]