CLONING AND SEQUENCING OF THE CDNA-ENCODING AN ISOFORM OF MICROTUBULE-ASSOCIATED PROTEIN TAU CONTAINING 4 TANDEM REPEATS - DIFFERENTIAL EXPRESSION OF TAU PROTEIN MESSENGER-RNAS IN HUMAN-BRAIN
CLONING AND SEQUENCING OF THE CDNA-ENCODING AN ISOFORM OF MICROTUBULE-ASSOCIATED PROTEIN TAU CONTAINING 4 TANDEM REPEATS - DIFFERENTIAL EXPRESSION OF TAU PROTEIN MESSENGER-RNAS IN HUMAN-BRAIN
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DOI：
10.1002/j.1460-2075.1989.tb03390.x
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发表时间：
1989-02-01
期刊：
影响因子：
11.4
通讯作者：
CROWTHER, RA
中科院分区：
文献类型：
--
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
我们已经分离出编码383个氨基酸的人类微管相关蛋白tau亚型的cDNA克隆。它与先前确定的tau序列的不同之处在于存在额外的31个氨基酸的重复序列，在其羧基末端的一半中有四个而不是三个串联重复序列。额外的重复序列由一个单独的外显子编码。探针来自cDNA克隆编码的三个（I型）和四个重复（II型）tau蛋白亚型检测mRNA的两种形式在所有adlut人的大脑区域检查。而在胎脑中仅发现I型mRNA，I型和II型mRNA存在于大脑皮质的锥体细胞中。在海马结构中，I型mRNA被发现在锥体细胞和颗粒细胞; II型mRNA被检测到在大多数，但不是全部，锥体细胞，但不是在颗粒细胞。这些观察结果表明tau蛋白mRNA以阶段特异性和细胞特异性方式表达。Tau蛋白存在于成对螺旋丝的蛋白酶抗性核心中，成对螺旋丝的主要组成核心，阿尔茨海默病中神经系统缠结的主要组成部分。与以前的研究结果相结合，目前的结果表明，三个和四个重复含有tau蛋白亚型存在于成对的螺旋丝的核心。
We have isolated cDNA clones encoding a 383-amino acid isoform of the human microtubule-associated protein tau. It differs from previously determined tau sequences by the presence of an additional repeat of 31 amino acids, giving four, rather than three, tandem repeats in its carboxy-terminal half. The extra repeat is encoded by a separate exon. Probes derived from cDNA clones encoding the three (type I) and four repeat (type II) tau protein isoforms detected mRNAs for both forms in all adlut human brain areas examined. However, in foetal brain only type I mRNA was found. Type I and type II mRNAs were present in pyramidal cells in cerebral cortex. In the hippocampal formation, type I mRNA was found in pyramidal and granule cells; type II mRNA was detected in most, though not all, pyramidal cells but not in granule cells. These observations indicate that tau protein mRNAs are expressed in a stage- and cell-specific manner. Tau protein is found in the protease-resistant core of the paired helical filament, the major constituent core of the paired helical filament, the major constituent of the neurofibrillary tangle in Alzheimer''s disease. Taken in conjunction with previous findings, the present results indicate that both the three and four repeat-containing tau protein isoforms are present in the core of the paired helical filament.