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The Journal of Neuroscience, January 1, 1998, 18(1):307-318
Platelet-Activating Factor Receptor Stimulation Disrupts Neuronal
Migration In Vitro
Gregory J.
Bix1 and
Gary D.
Clark1, 2
Departments of
1 Pediatrics, Neurology, and
2 Neuroscience, The Cain Foundation Laboratories, Baylor College of Medicine, Houston,
Texas 77030
LIS-1 is a gene whose hemi-deletion causes the
human neuronal migration disorder Miller-Dieker lissencephaly. It
encodes a subunit of a brain platelet-activating factor (PAF)
acetylhydrolase, an enzyme that inactivates PAF by hydrolyzing the
acetyl moiety in the sn2 position of this phospholipid.
Because PAF receptor activation has been shown to affect the developing
neuronal cytoskeleton, we have hypothesized that a role for PAF in
neurodevelopment is that of a modulator of neuroblast movement (a
cytoskeletal function) and that an aberrant regulation of PAF could
lead to an early arrest in migration. This report examines the effects
of the nonhydrolyzable PAF receptor agonist methyl carbamyl PAF
(mc-PAF) on the unidirectional in vitro migration of
granule cells from cerebellar cell reaggregates on a laminin substrate.
Bath treatment with mc-PAF yields a dose-dependent decrease in granule
cell migration compared with controls. This effect can be blocked by
the simultaneous bath application of BN 52021 and
trans-BTD, PAF receptor-specific antagonists. Although mc-PAF minimally inhibited neurite growth, its primary effect was on
somal movement along preextended neurites. These experiments suggest
that the stimulation of neuronal PAF receptors could be one crucial
step for the regulation of neuroblast migration and that disturbed PAF
catabolism during neurodevelopment could contribute to the neuronal
migration defects observed in Miller-Dieker lissencephaly.
Key words:
methyl carbamyl platelet-activating factor (mc-PAF); BN
52021; platelet-activating factor (PAF); neuronal migration; Miller-Dieker lissencephaly; LIS-1; PAF acetylhydrolase; PAF
receptor
Copyright © 1998 Society for Neuroscience 0270-6474/98/181307-12$05.00/0
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