A cilium-independent role for intraflagellar transport 88 in regulating angiogenesis  

IFT88以非依赖于纤毛的方式调控血管新生

作　　者：Yang Yang Miao Chen Jingrui Li Renjie Hong Jia Yang Fan Yu Te Li Song Yang Jie Ran Chunyue Guo Yi Zhao Yi Luan Min Liu Dengwen Li Songbo Xie Jun Zhou 杨阳;陈苗;李敬瑞;洪仁杰;杨佳;于凡;李特;杨松;冉杰;郭春月;赵毅;栾一;刘敏;李登文;谢松波;周军

机构地区：[1]College of Life Sciences,State Key Laboratory of Medicinal Chemical Biology,Key Laboratory of Bioactive Materials of the Ministry of Education,Tianjin Key Laboratory of Protein Science,Nankai University,Tianjin 300071,China [2]College of Life Sciences,Shandong Provincial Key Laboratory of Animal Resistance Biology,Collaborative Innovation Center of Cell Biology in Universities of Shandong,Institute of Biomedical Sciences,Shandong Normal University,Jinan 250014,China [3]Department of Translational Medicine Center,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China

出　　处：《Science Bulletin》2021年第7期727-739,M0004,共14页科学通报（英文版）

基　　金：supported by grants from the National Key R&D Program of China(2017YFA0503502);the National Natural Science Foundation of China(31730050,31871347,and 31900502)。

摘　　要：Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellar transport 88(IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with c-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.血管新生是一个复杂的生物学过程,涉及血管内皮细胞的众多活动,对于不少生理和病理过程至关重要.但是,血管新生的调控机制尚不清楚.本研究发现,在纤毛形成中发挥关键作用的蛋白IFT88对于小鼠体内的血管新生十分重要,并且IFT88对血管新生的调控并不依赖于该蛋白在纤毛形成中的作用. IFT88通过与γ微管蛋白、微管正端示踪蛋白等微管结合蛋白相互作用,调节微管的结构特性.进一步,通过免疫荧光显微分析、活细胞成像等手段,发现IFT88调节血管内皮细胞的极化,促进细胞的定向迁移;并发现在血管内皮细胞分裂时, IFT88增强纺锤体星体微管的稳定性,从而有利于纺锤体定向和细胞的定向分裂.本研究揭示IFT88以非依赖于纤毛的方式调节血管内皮细胞活动,促进了对血管新生调控机制的理解.

关 键 词：IFT88 ANGIOGENESIS CILIUM Cell migration Cell division Microtubule stability 

分 类 号：Q463[生物学—生理学]