Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain.
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 (alpha1 and alpha2) 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 alpha2 and beta subunit were detected in the adult brain by Western blotting. Biochemical analyses revealed that the alpha1/alpha2 heterodimer and alpha2/alpha2 homodimer are major catalytic units of embryonic and adult brain PAF acetylhydrolases, respectively. The alpha1 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 alpha1 protein were expressed only in neurons but not in glial cells and fibroblasts. In contrast, alpha2 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 alpha1 expression is restricted to actively migrating neurons in rats and that switching of catalytic subunits from the alpha1/alpha2 heterodimer to the alpha2/alpha2 homodimer occurred in these cells during brain development, suggesting that PAF acetylhydrolase plays a role(s) in neuronal migration.
Manya
H
H
Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Aoki
J
J
Watanabe
M
M
Adachi
T
T
Asou
H
H
Inoue
Y
Y
Arai
H
H
Inoue
K
K
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000254:growth & development*; D002384:Catalysis; D002417:Cattle; D004926:Escherichia coli; D009474:Neurons / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats
D010972:Platelet Activating Factor; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase