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J Biol Chem, Vol. 273, Issue 29, 18567-18572, July 17, 1998

Switching of Platelet-activating Factor Acetylhydrolase Catalytic Subunits in Developing Rat Brain

Hiroshi ManyaDagger , Junken AokiDagger , Masahiko Watanabe§, Tomoya AdachiDagger , Hiroaki Asou, Yoshirou Inoue§, Hiroyuki AraiDagger , and Keizo InoueDagger

From the Dagger  Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan, the § Laboratory of Molecular Neuroanatomy, Division of Brain Science, Graduate School of Medicine, Hokkaido University, Sapporo 060, Japan, and the  Department of Cell Biology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173, Japan

In a previous study, we demonstrated that Platelet-activating Factor (PAF) acetylhydrolase purified from bovine brain cortical cytosol consists of two mutually homologous catalytic subunits (alpha 1 and alpha 2) and one putative regulatory beta  subunit. The latter is a product of the LIS1 gene, which is defective in the Miller-Dieker syndrome, a form of lissencephaly. In this study, we examined the expression patterns of these three subunits in the developing rat brain. All three subunits were expressed in embryonic brain, whereas only alpha 2 and beta  subunit were detected in the adult brain by Western blotting. Biochemical analyses revealed that the alpha 1/alpha 2 heterodimer and alpha 2/alpha 2 homodimer are major catalytic units of embryonic and adult brain PAF acetylhydrolases, respectively. The alpha 1 transcript and protein were detected predominantly in embryonic and postnatal neural tissues, such as the brain and spinal cord. Furthermore, we found using primary cultured cells isolated from neonatal rat brain that alpha 1 protein were expressed only in neurons but not in glial cells and fibroblasts. In contrast, alpha 2 and beta  transcripts and proteins were detected both in neural and non-neural tissues, and their expression level was almost constant from fetal stages through adulthood. These results indicate that alpha 1 expression is restricted to actively migrating neurons in rats and that switching of catalytic subunits from the alpha 1/alpha 2 heterodimer to the alpha 2/alpha 2 homodimer occurred in these cells during brain development, suggesting that PAF acetylhydrolase plays a role(s) in neuronal migration.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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