Em. Quinlan et S. Halpain, EMERGENCE OF ACTIVITY-DEPENDENT, BIDIRECTIONAL CONTROL OF MICROTUBULE-ASSOCIATED PROTEIN MAP2 PHOSPHORYLATION DURING POSTNATAL-DEVELOPMENT, The Journal of neuroscience, 16(23), 1996, pp. 7627-7637
Pronounced changes in neuronal morphology occur as synapses mature; ho
wever, little is known about how synaptic transmission regulates the d
eveloping neuronal cytoskeleton. The postsynaptic, microtubule-associa
ted protein MAP:! is a target of multiple, calcium-dependent signaling
pathways activated by synaptic transmission. Here we demonstrate that
MAP2 phosphorylation is differentially regulated across development.
In P-32-labeled hippocampal slices prepared from adult rats, depolariz
ation stimulated a bidirectional change in the phosphorylation of immu
noprecipitated MAP2. A transient increase was mediated by metabotropic
glutamate receptors (mGluRs) and stimulation of mitogen-activated pro
tein kinases (MAPKs), Ca2+/calmodulin-dependent protein kinases (CaMKs
), and protein kinase C (PKC). This increase was followed by a persist
ent dephosphorylation mediated by NMDA receptors and activation of pro
tein phosphatase 2B (PP2B or calcineurin). in contrast, depolarization
of neonatal hippocampal slices stimulated exclusively a net increase
in MAP2 phosphorylation, which was attenuated by inhibitors of MAPKs,
but not CaMKs or PKC. Furthermore, although incubation in NMDA induced
a time-dependent decrease in MAP2 phosphorylation in both adults and
neonates, this effect was both less robust and less sensitive to calci
neurin inhibitors in neonates than in adults. These data indicate that
the mechanisms coupling glutamate release to MAP2 dephosphorylation a
re relatively lacking in the neonatal hippocampus. Highly phosphorylat
ed MAP2 is impaired in its ability to stabilize microtubules and actin
filament bundles in vitro. The neonatal propensity toward glutamate-s
timulated MAP2 phosphorylation may serve to reduce cytoskeletal stabil
ity and permit dendritic arborization early in postnatal development.
In mature neurons, the bidirectional control of MAP2 phosphorylation m
ay participate in activity-dependent synaptic remodeling.