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 terminals. In transgenic mice, overexpression of GAP-43 leads to the spontaneous formation of new synapses and enhanced sprouting after injury. Null mutation of the GAP-43 gene disrupts axonal pathfinding and is generally lethal shortly after birth. Manipulations of GAP-43 expression likewise have profound effects on neurite outgrowth for cells in culture. GAP-43 appears to be involved in transducing intra- and extracellular signals to regulate cytoskeletal organization in the nerve ending. Phosphorylation by protein kinase C is particularly significant in this regard, and is linked with both nerve-terminal sprouting and long-term potentiation. In the brains of humans and other primates, high levels of GAP-43 persist in neocortical association areas and in the limbic system throughout life, where the protein might play an important role in mediating experience-dependent plasticity.
Benowitz
L I
LI
Children's Hospital, Dept of Surgery, Boston, MA, USA.
Routtenberg
A
A
D000818:Animals; D001921:Brain / Q000254:growth & development*; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*
D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins