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哺乳动物中枢神经系统细胞中髓鞘相关神经突抑制因子Nogo - A及其受体Nogo - 受体的定位与表达

Localisation and expression of a myelin associated neurite inhibitor, Nogo-A and its receptor Nogo-receptor by mammalian CNS cells.

作者信息

Nyatia E, Lang D M

机构信息

Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.

出版信息

Res Vet Sci. 2007 Dec;83(3):287-301. doi: 10.1016/j.rvsc.2007.01.011. Epub 2007 Apr 10.

DOI:10.1016/j.rvsc.2007.01.011
PMID:17428512
Abstract

Axon regeneration failure in the adult mammalian central nervous system (CNS) is partly due to inhibitory molecules associated with myelin. The Nogo receptor (NgR) plays a role in this process through an extraordinary degree of cross reactivity with three structurally unrelated myelin-associated inhibitory ligands namely; Nogo-A, myelin associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp). The major aim of the study was to investigate and explore the cellular localisation and expression pattern of NgR and Nogo-A in the mammalian nervous system. We therefore generated a rabbit polyclonal anti-NgR antibody from the leucine rich repeat (LRR) No. 9 domain of the NgR polypeptide chain. Together with a commercially available polyclonal antibody specific for NgR, and in conjunction with double labeling immunofluorescence methods on cryosections and cell cultures, NgR immunoreactivity was observed in the CNS and dorsal root ganglia (DRG). In cellular populations, it was confined to neuronal cell bodies and their processes. NgR was also localised on the surface of extending DRG intact axons and growth cones in live staining experiments. Nogo-A, a member of the reticulon family protein, was widely distributed in the mammalian brain, spinal cord, and DRG. Intense Nogo-A immunoreactivity was also detected in oligodendrocyte cell bodies and their myelin sheaths in nerve fibre tracts of the CNS. Furthermore, numerous populations of neurons in the brain and spinal cord expressed Nogo-A to a variable extent in their cell bodies and neurites, suggesting additional, as-yet-unknown, functions of this protein. These results confirm results obtained by other researchers with different sets of antibodies. However, they also raise the question of the mechanism and circumstances under which NgR interacts with Nogo-A, as the latter appears to be confined to the cytoplasm and can therefore not be expected to bind NgR on the axon surface.

摘要

成年哺乳动物中枢神经系统(CNS)中轴突再生失败部分归因于与髓磷脂相关的抑制分子。Nogo受体(NgR)通过与三种结构不相关的髓磷脂相关抑制配体(即Nogo-A、髓磷脂相关糖蛋白(MAG)和少突胶质细胞髓磷脂糖蛋白(OMgp))具有非凡程度的交叉反应性,在这一过程中发挥作用。该研究的主要目的是调查和探索NgR和Nogo-A在哺乳动物神经系统中的细胞定位和表达模式。因此,我们从NgR多肽链的富含亮氨酸重复序列(LRR)第9结构域制备了兔多克隆抗NgR抗体。与市售的针对NgR的多克隆抗体一起,结合对冷冻切片和细胞培养物的双标记免疫荧光方法,在中枢神经系统和背根神经节(DRG)中观察到了NgR免疫反应性。在细胞群体中,它局限于神经元细胞体及其突起。在活细胞染色实验中,NgR也定位于延伸的DRG完整轴突和生长锥的表面。Nogo-A是网状蛋白家族蛋白的成员,广泛分布于哺乳动物的脑、脊髓和DRG中。在中枢神经系统神经纤维束的少突胶质细胞体及其髓鞘中也检测到强烈的Nogo-A免疫反应性。此外,脑和脊髓中的许多神经元群体在其细胞体和神经突中不同程度地表达Nogo-A,这表明该蛋白还有其他尚未知晓的功能。这些结果证实了其他研究人员使用不同抗体组所获得的结果。然而,它们也提出了NgR与Nogo-A相互作用的机制和情况的问题,因为后者似乎局限于细胞质中,因此预计不会与轴突表面的NgR结合。

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