MILLER-DIEKER LISSENCEPHALY GENE ENCODES A SUBUNIT OF BRAIN PLATELET-ACTIVATING-FACTOR
MILLER-DIEKER LISSENCEPHALY GENE ENCODES A SUBUNIT OF BRAIN PLATELET-ACTIVATING-FACTOR
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DOI：
10.1038/370216a0
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发表时间：
1994-07-21
期刊：
影响因子：
64.8
通讯作者：
INOUE, K
中科院分区：
文献类型：
--
作者：
HATTORI, M;ADACHI, H;INOUE, K
血小板活化因子（PAF）参与多种生物和病理过程(1)，PAF乙酰水解酶广泛分布于血浆和组织细胞质中（2,3），该酶通过去除n-2位置的乙酰基使PAF失活。PAP乙酰水解酶的一种异质三聚体存在于牛脑皮层中，其亚基的相对分子质量分别为45K、30K和29K（参考文献4）。我们现在已经分离出了45K亚基的互补DNA。序列分析显示，该亚基与MiUer-Dieker无裂脑畸形（MiUer-Dieker lisissencephaly）的致病基因（LIS-1）编码的蛋白质惊人地一致（99%）(5)，MiUer-Dieker无裂脑畸形是一种人类大脑畸形，表现为大脑表面光滑和异常的神经元迁移。这表明LIS-1基因产物是细胞内PAF乙酰水解酶45K亚基的人类同源物。我们的结果提出了在分化和发育过程中PAF和PAF乙酰水解酶在脑皮层形成中起重要作用的可能性。
PLATELET-ACTIVATING factor (PAF) is involved in a variety of biological and pathological processes(1) and PAF acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position, is widely distributed in plasma and tissue cytosols(2,3). One isoform of PAP acetylhydrolase present in bovine brain cortex is a heterotrimer comprising subunits with relative molecular masses of 45K, 30K and 29K (ref. 4). We have now isolated the complementary DNA for the 45K subunit. Sequence analysis revealed a striking identity (99%) of the subunit with a protein encoded by the causative gene (LIS-1) for MiUer-Dieker lissencephaly(5), a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration. This indicates that the LIS-1 gene product is a human homologue of the 45K subunit of intracellular PAF acetylhydrolase. Our results raise the possibility that PAF and PAF acetylhydrolase are important in the formation of the brain cortex during differentiation and development.