IDENTIFICATION, SECRETION, AND NEURAL EXPRESSION OF APPL, A DROSOPHILA PROTEIN SIMILAR TO HUMAN AMYLOID PROTEIN-PRECURSOR
IDENTIFICATION, SECRETION, AND NEURAL EXPRESSION OF APPL, A DROSOPHILA PROTEIN SIMILAR TO HUMAN AMYLOID PROTEIN-PRECURSOR
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DOI：
10.1523/jneurosci.10-12-03849.1990
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发表时间：
1990-12-01
影响因子：
5.3
通讯作者：
WHITE, K
中科院分区：
文献类型：
--
作者：
LUO, LQ;MARTINMORRIS, LE;WHITE, K
最近发现了一个果蝇基因[淀粉样蛋白前体样（Appl）]，其预测氨基酸序列（Appl）与阿尔茨海默病相关的β -淀粉样蛋白前体（APP）具有广泛的同源性。对Appl基因编码的蛋白进行表征的初衷是希望这个简单的模型系统能够帮助阐明Appl和APP蛋白提供的基本功能。在本报告中，我们在胚胎提取物、原代培养物和转染细胞中鉴定了2种形式的APPL蛋白。APPL作为145 kda的膜相关前体合成，转化为130 kda的分泌形式，缺乏细胞质结构域。两种形式都是n -糖基化的。脉冲追踪和亚细胞定位研究表明，这种转换非常迅速。APP和APPL生物发生的相似性进一步证明了APPL和APP可能在功能上是同源的，其分泌事件具有生理意义。免疫细胞化学研究表明，APPL蛋白首先在伴随轴突发生的发育神经元中被检测到，并且仍然与分化的神经元有关。在神经元细胞体、轴突束和神经区观察到APPL的免疫反应性。在胚胎中，APPL蛋白仅在CNS和PNS神经元中表达，这与苹果转录物的定位一致。APPL蛋白的表达模式表明该蛋白在神经系统中具有祖先功能。
A Drosophila gene [amyloid protein precursor-like (Appl)] has recently been identified whose predicted amino acid sequence (APPL) shares extensive homology with the beta-amyloid protein precursor (APP) associated with Alzheimer's disease. Characterization of proteins encoded by the Appl gene was initiated with the expectation that this simple model system might help elucidate the basic function provided by APPL and APP proteins.In this report, we identify 2 forms of the APPL protein in embryonic extracts, primary cultures, and transfected cells. APPL is synthesized as a 145-kDa membrane-associated precursor that is converted to a 130-kDa secreted form that lacks the cytoplasmic domain. Both forms are N-glycosylated. Pulse-chase and subcellular localization studies suggest that the conversion is very rapid. The similarities of biogenesis between APP and APPL provide further evidence that APPL and APP might be functionally homologous, and that the secretion event is of physiological significance.Immunocytochemicals studies show that the APPL proteins are first detected in developing neurons concomitant with axonogenesis and remain associated with differentiated neurons. APPL immunoreactivity was observed in neuronal cell bodies, axonal tracts, and neuropil regions. In the embryo, APPL proteins are expressed exclusively in the CNS and PNS neurons, consistent with the Appl transcript localization. The expression pattern of APPL proteins suggests an ancestral function for this protein in the nervous system.