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Ehk-1(一种大脑中的神经元Elk样受体酪氨酸激酶)的表达及发育调控

Expression and developmental regulation of Ehk-1, a neuronal Elk-like receptor tyrosine kinase in brain.

作者信息

Taylor V, Miescher G C, Pfarr S, Honegger P, Breitschopf H, Lassmann H, Steck A J

机构信息

Neurological Clinic and Research Department, University Hospital, Basel, Switzerland.

出版信息

Neuroscience. 1994 Nov;63(1):163-78. doi: 10.1016/0306-4522(94)90014-0.

Abstract

Protein tyrosine kinases are pivotal in central nervous tissue development and maintenance. Here we focus on the expression of Ehk-1, a novel Elk-related receptor tyrosine kinase. Ehk-1 gene expression is observed in the developing and adult central nervous system and is highly regulated throughout development at both the messenger RNA and protein levels. Three messenger RNA transcripts of 8.5, 5.9 and 5.1 kb are detectable in the rat brain and a variety of splice possibilities have been identified. However, a major protein species of around M(r) 120,000 predominates throughout development. Ehk-1 messenger RNA and protein levels are highest in the first postnatal week. By in situ messenger RNA hybridization the gene is expressed by all neurons of the adult brain, but mostly in the hippocampus, cerebral cortex and large neurons of the deep cerebellar nuclei, as well as the Purkinje and granular cells of the cerebellum. At earlier stages of development, transcripts are most prominent in the periventricular germinal layers of the brain. Immunohistochemistry reveals a pronounced membrane associated protein expression in immature neurons. In the adult animal, peak reactivity was found in the neuropil with sparing of most perikarya. The spatial and temporal pattern of ehk-1 gene expression suggests a role in both the development and maintenance of differentiated neurons of the central nervous system.

摘要

蛋白酪氨酸激酶在中枢神经组织的发育和维持过程中起着关键作用。在此,我们聚焦于一种新型的Elk相关受体酪氨酸激酶Ehk-1的表达情况。在发育中的和成年的中枢神经系统中均可观察到Ehk-1基因的表达,并且在整个发育过程中,其在信使核糖核酸(mRNA)和蛋白质水平上均受到高度调控。在大鼠脑中可检测到8.5、5.9和5.1 kb的三种信使核糖核酸转录本,并且已确定了多种剪接可能性。然而,在整个发育过程中,主要的蛋白质种类的相对分子质量约为120,000。Ehk-1信使核糖核酸和蛋白质水平在出生后的第一周最高。通过原位信使核糖核酸杂交技术发现,该基因在成体脑的所有神经元中均有表达,但主要存在于海马体、大脑皮层、小脑深部核团的大神经元以及小脑的浦肯野细胞和颗粒细胞中。在发育的早期阶段,转录本在脑室周围的生发层中最为显著。免疫组织化学显示,在未成熟神经元中存在明显的膜相关蛋白表达。在成年动物中,在神经纤维网中发现了最强的反应性,而大多数神经细胞体则未受影响。Ehk-1基因表达的时空模式表明其在中枢神经系统分化神经元的发育和维持过程中均发挥作用。

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