STRUCTURE AND DEVELOPMENTAL EXPRESSION OF THE NERVE GROWTH-FACTOR RECEPTOR IN THE CHICKEN CENTRAL NERVOUS-SYSTEM

STRUCTURE AND DEVELOPMENTAL EXPRESSION OF THE NERVE GROWTH-FACTOR RECEPTOR IN THE CHICKEN CENTRAL NERVOUS-SYSTEM
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DOI:
10.1016/0896-6273(89)90179-7
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发表时间:
1989-02-01
期刊:
影响因子:
16.2
通讯作者:
REICHARDT, LF
REICHARDT, LF
中科院分区:
医学1区
文献类型:
--
作者:
LARGE, TH;WESKAMP, G;REICHARDT, LF

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鸡神经生长因子(NGF)受体cdna已被分离和测序,以确定功能重要的受体结构域,并作为确定NCF受体在早期胚胎发生中的功能的第一步。比较鸟类和哺乳动物NCF受体的初级氨基酸序列,发现了几个在保护程度上不同的离散结构域。高度保守的区域包括一个可能参与配体结合的胞外结构域,其中24个半胱氨酸残基和几乎所有带负电荷的残基的位置是保守的;一种跨膜区域,包括细胞外和细胞质氨基酸的两侧延伸,其特性表明它与其他蛋白质相互作用;细胞质的PEST序列,可能调节受体的转换。在发育中的中枢神经系统的许多区域都发现了NGF受体mRNA的瞬时表达。实验表明,神经生长因子及其受体都有助于调节视网膜的发育。在过去的35年中,神经生长因子(NGF)在周围感觉和交感神经元的存活和发育中的关键作用已经得到了很好的描述(Levi-Montalcini, 1987)。最近的研究表明,NGF也可能对哺乳动物基底前脑的内在(Mobley et al., 1985)和投射胆碱能神经元的发育和维持很重要(Gnahn et al., 1983; Williams et al., 1986; Hefti, 1986)。这些外周和中枢神经元支配的组织已被证明可以合成神经生长因子,这支持了神经生长因子在很大程度上是靶源性营养因子的经典模型(Shelton和Reichardt, 1984,1986; Heumann等人,1984;Korsching等人,1985;Whittemore等人,1986;large等人,1986;Davies等人,1987;yer- lelievre等人,1988)。NGF还可能对发育中的神经系统内的多种其他细胞类型产生影响,因为在许多鸟类和哺乳动物中枢神经系统细胞核发育的早期就发现了NGF的结合位点
Chicken nerve growth factor (NGF) receptor cDNAs have been isolated and sequenced in an effort to identify functionally important receptor domains and as an initial step in determining the functions of the NCF receptor in early embryogenesis. Comparisons of the primary amino acid sequences of the avian and mammalian NCF receptors have identified several discrete domains that differ in their degree of conservation. The highly conserved regions include an extracellular domain, likely to be involved in ligand binding, in which the positions of 24 cysteine residues and virtually all negatively charged residues are conserved; a transmembrane region, including flanking stretches of extracellular and cytoplasmic amino acids, which has properties suggesting it interacts with other proteins; and a cytoplasmic PEST sequence, which may regulate receptor turnover. Transient expression of NGF receptor mRNA has been seen in many regions of the developing CNS. Experiments suggest that both NGF and its receptor help regulate development of the retina. tntroductionThe critical role of nerve growth factor (NGF) in the survival and development of peripheral sensory and sympathetic neurons has been well characterized over the past 35 years (Levi-Montalcini, 1987). Recent studies have indicated that NGF also may be important for the development and maintenance of intrinsic(Mobley et al., 1985) and projection cholinergic neurons in the basal forebrain of mammals(Gnahn et al., 1983; Williams et al., 1986; Hefti, 1986). The tissues innervated by these peripheral and central neurons have been shown to synthesize NGF, supporting the classic model that NGF, in large part, is a target-derived trophic factor (Shelton and Reichardt, 1984, 1986; Heumann et al., 1984; Korsching et al., 1985; Whittemore et al., 1986; Large et al., 1986; Davies et al., 1987; Ayer-LeLievre et al., 1988). NGF also may have effects on a variety of additional cell types within the developing nervous system since NGF binding sites have been detected early in the development of many avian and mammalian CNS nuclei