首页> 外文期刊>Cell motility and the cytoskeleton >Mammalian Navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions.
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Mammalian Navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions.

机译:哺乳动物导航器是微管正末尾追踪蛋白,可以重组细胞骨架以诱导神经突样延伸。

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摘要

Mammalian microtubule plus-end tracking proteins (+TIPs) specifically associate with the ends of growing microtubules. +TIPs are involved in many cellular processes, including mitosis, cell migration and neurite extension. Navigators are mammalian homologues of the C. elegans unc-53 protein, an ATPase that has been linked to the migration and outgrowth of muscles, axons and excretory canals. Here we show that all three mammalian Navigators are +TIPs, consistent with a previous study on Navigator 1 (NAV1) (Martinez-Lopez et al., Mol Cell Neurosci 2005;28:599-612). Overexpression of GFP-tagged Navigators causes displacement of CAP_GLY-motif containing +TIPs, such as CLIP-170, from microtubule ends, suggesting that the Navigator-binding sites on microtubule ends overlap with those of the CAP_GLY-motif proteins. In interphase cells, mammalian Navigators also prominently localize to centrosomes, a localization that does not depend on an intact microtubule network. Fluorescence recovery after photobleaching (FRAP) experiments indicate that NAV1 associates with intracellular structures other than microtubules or centrosomes. Expression of GFP-tagged Navigators induces the formation of neurite-like extensions in non-neuronal cells, showing that Navigators can dominantly alter cytoskeletal behavior. For NAV1 this function depends on its ATPase activity; it is not achieved by a classical type of MT bundling and stabilization. Combined our data suggest that Navigators are +TIPs that can reorganize the cytoskeleton to guide cell shape changes. Our data are consistent with a role for Navigators in neurite outgrowth.
机译:哺乳动物微管正向末端追踪蛋白(+ TIP)与生长中的微管末端特异性结合。 + TIPs参与许多细胞过程,包括有丝分裂,细胞迁移和神经突延伸。导航员是秀丽隐杆线虫unc-53蛋白的哺乳动物同源物,秀丽隐杆线虫unc-53蛋白是一种与肌肉,轴突和排泄管的迁移和生长相关的ATPase。在这里,我们显示所有三个哺乳动物导航器都是+ TIP,与先前对导航器1(NAV1)的研究一致(Martinez-Lopez等人,Mol Cell Neurosci 2005; 28:599-612)。 GFP标记的Navigators的过表达导致含有+ TIP的CAP_GLY-motif(例如CLIP-170)从微管末端移出,这表明微管末端的Navigator-结合位点与CAP_GLY-motif蛋白重叠。在相间细胞中,哺乳动物导航器也显着地定位于中心体,该定位不依赖于完整的微管网络。光漂白(FRAP)实验后的荧光恢复表明NAV1与除微管或中心体以外的细胞内结构相关。带有GFP标记的Navigators的表达诱导了非神经元细胞中神经突样延伸的形成,这表明Navigators可以显着改变细胞骨架的行为。对于NAV1,此功能取决于其ATPase活性。经典的MT捆绑和稳定无法实现这一目标。结合我们的数据表明,导航仪是+ TIP,可以重组细胞骨架以指导细胞形状的变化。我们的数据与导航员在神经突增生中的作用一致。

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