Cep170 於神經突之非中心體分佈及其促使神經突生長之研究

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Cep170 於神经突之非中心体分布及其促使神经突生长之研究

Cep170 localizes as non-centrosomal puncta along the neurite and promotes neurite elongation

吴佳佳 , 硕士　　导师：黄兆祺　　

英文

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摘要 │ 参考文献 (69) │ 国际计量

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Microtubule is the major cytoskeleton in neurons and involved in numerous developmental processes. In a previous study, quantitative proteomics has been used to examine microtubule-associated proteomes in mouse embryonal carcinoma cells before and after neuronal differentiation. The centrosome protein Cep170, which made up part of the mitotic centrosome, has been found to exhibit a significant increase on microtubules upon neuronal differentiation. Overexpressing Cep170 caused a significant increase in neurite length in both P19 cell-derived neurons and mouse hippocampal neurons, suggesting that Cep170 is involved in the regulation of neuronal morphogenesis. However, the exact mechanism of Cep170 in controlling the morphogenetic process of neurons remain elusive. In this study, we attempt to answer the aforementioned question by studying the effect of Cep170 overexpression on microtubule cytoskeleton as well as examining the localization of endogenous Cep170. We discovered that overexpressing Cep170 causes a significant increase in both axon and dendrite length in dissociated hippocampal neurons. Overexpressed Cep170 localizes as non-centrosomal puncta along both axons and dendrites, and displays variation in morphology in different regions of the neurite. In addition, overexpressed Cep170 is enriched at axon but not dendrite tips. Furthermore, overexpressing Cep170 in hippocampal neurons increases the microtubule polymerization rate. We also attempted to determine the localization of the endogenous Cep170 in neurons by immunofluorescence staining. Consistent with the overexpression study, endogenous Cep170 also localizes as non-centrosomal puncta along the neurite with a significant enrichment at the axon tip. Our results suggest that Cep170 localizes as non-centrosomal puncta in post-mitotic cells and its effect on microtubule polymerization rate may be the mechanism in promoting neurite elongation.

参考文献 ( 69 ) 〈TOP〉

Ahmad, F. and Baas, P. (1995). Microtubules released from the neuronal centrosome are transported into the axon. Journal of Cell Science, 108(8), 2761-2769.
Andersen, J.S., Wilkinson, C.J., Mayor, T., Mortensen, P., Nigg, E.A., Mann, M. (2003). Proteomic characterization of the human centrosome by protein correlation profiling. Nature, 426, 570–574
Armijo-Weingart, L. and Gallo, G. (2017). It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches. Molecular and Cellular Neuroscience, 84, 36-47.
Baas, P. W., and Lin, S. (2011). Hooks and comets: The story of microtubule polarity orientation in the neuron. Developmental Neurobiology, 71(6), 403–418.
Baas, P.W., and F.J. Ahmad. (1993). The transport properties of axonal microtubules establish their polarity orientation. Journal of Cell Biology, 120, 1427-1437.

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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。