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Light-microscopic immunolocalization of the growth- and plasticity-associated protein GAP-43 in the developing rat
C B McGuire1, G J Snipes, J J Norden
1Department of Cell Biology, Vanderbilt University Medical School, Nashville, TN 37232.
Insights
Growth-associated protein-43 (GAP-43) is a neuron-specific protein crucial for axon growth during development. It is also involved in synaptic plasticity in the mature brain, suggesting a common regulatory mechanism.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Growth-associated protein-43 (GAP-43) is a developmentally regulated phosphoprotein.
- GAP-43 is synthesized and transported rapidly, particularly during neural development and synapse formation.
- It is a substrate for protein kinase C and identified as protein F1, regulated during hippocampal long-term potentiation.
Purpose of the Study:
- To characterize the cellular localization of GAP-43.
- To investigate the role of GAP-43 in neural development and synaptic plasticity.
Main Methods:
- Raised a specific antiserum against GAP-43.
- Used the antiserum as a probe for immunolocalization in rat brain tissue.
- Correlated GAP-43 localization with known areas of neural growth and synaptic plasticity.
Main Results:
- GAP-43 is neuron-specific.
- Localized to growing neuronal processes in developing rat brain.
- Found in presynaptic terminals of both peripheral and central nervous systems.
- Abundant in mature CNS neuropil, especially in cerebellum, neocortex, and hippocampus.
- High density in areas known for synaptic plasticity.
Conclusions:
- GAP-43 plays a role in axon growth during development.
- GAP-43 is implicated in synaptic plasticity in the mature central nervous system.
- Suggests a common mechanism involving protein kinase C-mediated phosphorylation of GAP-43 regulates both axon growth and synaptic plasticity.
Abstract:
Growth-associated protein-43 (GAP-43) is a developmentally regulated, fast-axonally transported phosphoprotein whose synthesis and transport are enhanced during periods of growth and synaptic terminal formation. GAP-43 is a substrate of protein kinase C and is identical to protein F1, a phosphoprotein which is regulated during long-term potentiation in the hippocampus. In order to characterize the cellular localization of GAP-43, we have raised a specific antiserum against it, and used this as a probe to show that GAP-43 is neuron-specific, and is localized to growing neuronal processes in developing rat brain, and to presynaptic terminals in both the peripheral and central nervous system. In the mature CNS, GAP-43 immunoreactivity is present in most neuropil areas, but is especially dense in the molecular layers of the cerebellum, neocortex, and the hippocampus, structures known to exhibit synaptic plasticity. Its localization, together with biochemical data concerning the dynamics of its synthesis and its identity as protein F1, suggest that GAP-43 may be involved in axon growth in the developing nervous system, and in some aspect of synaptic plasticity in the mature CNS. These data also suggest that axon growth and synaptic plasticity in the brain may be regulated by a common mechanism, both involving the protein kinase C-mediated phosphorylation of GAP-43.