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感觉神经节中p75受体的表达水平受靶组织中神经生长因子水平的调节。

Level of p75 receptor expression in sensory ganglia is modulated by NGF level in the target tissue.

作者信息

Kitzman P H, Perrone T N, LeMaster A M, Davis B M, Albers K M

机构信息

Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, Lexington 40536, USA.

出版信息

J Neurobiol. 1998 Jun;35(3):258-70. doi: 10.1002/(sici)1097-4695(19980605)35:3<258::aid-neu3>3.0.co;2-y.

Abstract

Neurotrophins play an essential role in sensory development by providing trophic support to neurons that innervate peripheral targets. Nerve growth factor (NGF), neurotrophin-3, neurotrophin-4, and brain-derived neurotrophin exert their survival effect by binding to two transmembrane receptor types: trk receptors, which exhibit binding specificity, and the p75NTR receptor, which binds all neurotrophins. To determine how target-derived neurotrophins affect sensory neuron development and function, we used transgenic mice that overexpress NGF in the skin to examine the impact of NGF overexpression on receptor expression. Previous studies of trk expression in trigeminal ganglia of adult NGF transgenics showed that the percentage of trkA neurons doubled and their number increased fivefold. The present study focused on the p75 receptor and shows that the percentage of neurons expressing p75NTR also increase in NGF ganglia, but only by 10%. This increase did not encompass the small, BS-IB-4 isolectin-positive cells as they remained p75 negative in transgenic ganglia. Interestingly, levels of trkA protein were not increased on a per-cell level, whereas levels of p75NTR increased nearly threefold. These results show that in sensory systems, target-derived NGF modulates the level of p75NTR receptor expression, and in so doing, may act to regulate the formation of functional receptor complexes and subsequent trophic action.

摘要

神经营养因子通过为支配外周靶标的神经元提供营养支持,在感觉发育中发挥着至关重要的作用。神经生长因子(NGF)、神经营养素-3、神经营养素-4和脑源性神经营养因子通过与两种跨膜受体类型结合发挥其存活作用:具有结合特异性的trk受体,以及能结合所有神经营养因子的p75NTR受体。为了确定靶源性神经营养因子如何影响感觉神经元的发育和功能,我们使用了在皮肤中过表达NGF的转基因小鼠,来研究NGF过表达对受体表达的影响。先前对成年NGF转基因小鼠三叉神经节中trk表达的研究表明,trkA神经元的百分比增加了一倍,其数量增加了五倍。本研究聚焦于p75受体,结果显示,在NGF神经节中,表达p75NTR的神经元百分比也有所增加,但仅增加了10%。这种增加并不包括小的、BS-IB-4异凝集素阳性细胞,因为它们在转基因神经节中仍为p75阴性。有趣的是,trkA蛋白的水平在单个细胞水平上并未增加,而p75NTR的水平却增加了近三倍。这些结果表明,在感觉系统中,靶源性NGF调节p75NTR受体的表达水平,进而可能调节功能性受体复合物的形成及随后的营养作用。

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