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大鼠成体脑内SCG10和p19/微管相关蛋白的信使核糖核酸的差异定位表明这些生长相关蛋白具有不同作用。

Differential localization of SCG10 and p19/stathmin messenger RNAs in adult rat brain indicates distinct roles for these growth-associated proteins.

作者信息

Himi T, Okazaki T, Wang H, McNeill T H, Mori N

机构信息

Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.

出版信息

Neuroscience. 1994 Jun;60(4):907-26. doi: 10.1016/0306-4522(94)90271-2.

Abstract

SCG10 is a developmentally regulated, growth-associated protein (GAP) that was isolated as a neuronal marker of the neural crest. It was recently found that SCG10 shares an amino acid sequence similarity with a phosphoprotein named stathmin or p19 of which phosphorylation is induced by nerve growth factor and vasoactive intestinal peptide in PC12 cells and striatal neurons, respectively. While expression of SCG10 messenger RNA dramatically decreases during postnatal development, significant levels of expression still persist into adulthood. To examine possible roles of SCG10 in the adult brain, we examined the distribution of messenger RNAs encoding SCG10 and p19/stathmin as well as GAP-43 in adult rat brain sections by northern blot, RNase protection and in situ hybridization. SCG10 transcripts are found at high levels in long-distance projecting neurons and neurons with extensive dendritic arbors, while p19/stathmin messenger RNA was weakly distributed over most brain areas. Both messenger RNAs are expressed in neuronal subpopulations but not in glia, although the overall distribution of the transcripts of these two structurally related genes is distinct. The spatial and temporal expression profiles of SCG10 messenger RNA is comparable to that of GAP-43, another neuronal GAP, in the developing nervous system, however the expression of SCG10 messenger RNA in the adult brain is distinct from that of GAP-43, especially in the hippocampus and brain stem, where the dentate granule cells and sensory and motor neurons of brainstem express SCG10 but not GAP-43. These results suggest that SCG10 may have a unique role in the neuronal growth-response of subsets of mature neurons, and that SCG10 plays a stathmin-like function at nerve terminals, to which it may be rapidly transported by means of membrane attachment due to a hydrophobic domain present in SCG10 but not in p19/stathmin. This suggests that SCG10 may play a role in structural plasticity in the adult brain.

摘要

SCG10是一种在发育过程中受调控的生长相关蛋白(GAP),最初作为神经嵴的神经元标志物被分离出来。最近发现,SCG10与一种名为stathmin或p19的磷蛋白具有氨基酸序列相似性,在PC12细胞和纹状体神经元中,该磷蛋白的磷酸化分别由神经生长因子和血管活性肠肽诱导。虽然SCG10信使核糖核酸(mRNA)的表达在出生后发育过程中显著下降,但仍有相当水平的表达持续到成年期。为了研究SCG10在成体大脑中的可能作用,我们通过Northern印迹法、核糖核酸酶保护法和原位杂交技术,检测了成年大鼠脑切片中编码SCG10、p19/stathmin以及GAP - 43的mRNA的分布情况。在长距离投射神经元和具有广泛树突分支的神经元中发现了高水平的SCG10转录本,而p19/stathmin信使核糖核酸在大多数脑区分布较弱。这两种信使核糖核酸均在神经元亚群中表达,但在胶质细胞中不表达,尽管这两个结构相关基因的转录本总体分布不同。在发育中的神经系统中,SCG10信使核糖核酸的时空表达谱与另一种神经元GAP即GAP - 43相当,然而在成体大脑中,SCG10信使核糖核酸的表达与GAP - 43不同,尤其是在海马体和脑干中,齿状颗粒细胞以及脑干的感觉和运动神经元表达SCG10但不表达GAP - 43。这些结果表明,SCG10可能在成熟神经元亚群的神经元生长反应中具有独特作用,并且SCG10在神经末梢发挥类似stathmin的功能,由于SCG10中存在但p19/stathmin中不存在的疏水结构域,它可能通过膜附着被快速转运至神经末梢。这表明SCG10可能在成体大脑的结构可塑性中发挥作用。

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