GAP-43 - AN INTRINSIC DETERMINANT OF NEURONAL DEVELOPMENT AND PLASTICITY

Several lines of investigation have helped clarify the role of GAP-43 (FI,B-50 or neuromodulin) in regulating the growth state of axon termi nals. In transgenic mice, overexpression of GAP-43 leads to the sponta neous formation of new synapses and enhanced sprouting after injury. N ull mutation of the GAP-43 gene disrupts axonal pathfinding and is gen erally lethal shortly after birth. Manipulations of GAP-43 expression likewise have profound effects on neurite outgrowth for cells in cultu re. GAP-43 appears to be involved in transducing intra- and extracellu lar signals to regulate cytoskeletal organization in the nerve ending. Phosphorylation by protein kinase C is particularly significant in th is regard, and is linked with both nerve-terminal sprouting and long-t erm potentiation. In the brains of humans and other primates, high lev els of GAP-43 persist in neocortical association areas and in the limb ic system throughout life, where the protein might play an important r ole in mediating experience-dependent plasticity.