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鸡的突触核蛋白:在发育胚胎中的克隆与表达。

Chicken synucleins: cloning and expression in the developing embryo.

作者信息

Tiunova A A, Anokhin K V, Saha A R, Schmidt O, Hanger D P, Anderton B H, Davies A M, Ninkina N N, Buchman V L

机构信息

P.K. Anokhin Institute of Normal Physiology, Baltyiskaya Street, Moscow, Russia.

出版信息

Mech Dev. 2000 Dec;99(1-2):195-8. doi: 10.1016/s0925-4773(00)00484-6.

Abstract

Synucleins comprise a family of small intracellular proteins that have recently attracted considerable attention because of their involvement in human diseases. Mutations of alpha-synuclein has been found in several families with hereditary early-onset Parkinson's disease and accumulation of this protein in characteristic cytoplasmic inclusions is a pathohistological hallmark of several neurodegenerative diseases that have been recently classified as 'alpha;-synucleinopathies' (reviewed in Brain Res. Bull. 50 (1999) 465; J. Neurosci. Res. 58 (1999) 120; Philos. Trans. R. Soc. Lond. Biol. Sci. 354 (1999) 1101; Brain Pathol. 9 (1999) 733). Aggregates of beta-synuclein and persyn (gamma-synuclein) also have been found in dystrophic neurites associated with Parkinson's and other neurodegenerative diseases (Proc. Natl. Acad. Sci. USA 96 (1999) 13450; and our unpublished observations). Moreover, persyn has been implicated in malignization of breast tumours (Cancer Res. 57 (1997) 759; Cancer Res. 59 (1999) 742; Hum. Mol. Genet. 7 (1998) 1417). All synucleins have distinct, although overlapping, patterns of expression in the embryonic, postnatal and adult mammalian nervous systems, suggesting important, although still not clear, biological functions in neuronal developing. Chicken embryo is a unique object for developmental studies that allows in vivo manipulations not always possible for mammalian embryos. Studies of synucleins expression in this model system could shed light on their functions in the developing nervous system. We cloned three chicken synucleins from the embryonic neural cDNA libraries and studied their expression in normal chicken embryonic tissues by Northern and in situ hybridization with specific probes. Our results demonstrate that primary structures and expression patterns of synucleins are similar in birds and mammals, suggesting that conserved function of synucleins is important for embryonic development of vertebrates.

摘要

突触核蛋白是一类小的细胞内蛋白质家族,由于它们与人类疾病有关,最近受到了相当多的关注。在几个患有遗传性早发性帕金森病的家族中发现了α-突触核蛋白的突变,并且这种蛋白质在特征性细胞质内含物中的积累是几种神经退行性疾病的病理组织学标志,这些疾病最近被归类为“α-突触核蛋白病”(见《脑研究通报》50 (1999) 465;《神经科学研究》58 (1999) 120;《英国皇家学会哲学学报B辑:生物科学》354 (1999) 1101;《脑病理学》9 (1999) 733中的综述)。在与帕金森病和其他神经退行性疾病相关的营养不良性神经突中也发现了β-突触核蛋白和persyn(γ-突触核蛋白)的聚集体(《美国国家科学院院刊》96 (1999) 13450;以及我们未发表的观察结果)。此外,persyn与乳腺肿瘤的恶性化有关(《癌症研究》57 (1997) 759;《癌症研究》59 (1999) 742;《人类分子遗传学》7 (1998) 1417)。所有突触核蛋白在胚胎、出生后和成年哺乳动物神经系统中都有独特但部分重叠的表达模式,这表明它们在神经元发育中具有重要但仍不清楚的生物学功能。鸡胚是发育研究的独特对象,它允许进行一些对哺乳动物胚胎来说不总是可行的体内操作。在这个模型系统中对突触核蛋白表达的研究可以揭示它们在发育中的神经系统中的功能。我们从胚胎神经cDNA文库中克隆了三种鸡突触核蛋白,并通过Northern杂交和用特异性探针进行原位杂交研究了它们在正常鸡胚组织中的表达。我们的结果表明,突触核蛋白的一级结构和表达模式在鸟类和哺乳动物中相似,这表明突触核蛋白的保守功能对脊椎动物的胚胎发育很重要。

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