Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase [corrected].
Platelet-activating factor (PAF) is involved in a variety of biological and pathological processes and PAF acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position, is widely distributed in plasma and tissue cytosols. One isoform of PAF 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 Miller-Dieker lissencephaly, 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.
Department of Health Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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M
Hattori
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Adachi
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M
Tsujimoto
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H
Arai
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K
Inoue
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002540:Cerebral Cortex / Q000002:abnormalities*; D000013:Congenital Abnormalities / Q000235:genetics; D018076:DNA, Complementary; D006801:Humans; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000235:genetics*; D010972:Platelet Activating Factor / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D010972:Platelet Activating Factor; D011506:Proteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human