GAP-43 as a plasticity protein in neuronal form and repair.
Neurons exhibit a remarkable plasticity of form, both during neural development and during the subsequent remodelling of synaptic connectivity. Here we review work on GAP-43 and G0, and focus upon the thesis that their interaction may endow neurons with such plasticity. We also present new data on the role of G proteins in neurite growth, and on the interaction of GAP-43 and actin. GAP-43 is a protein induced during periods of axonal extension and highly enriched on the inner surface of the growth cone membrane. Its membrane localization is primarily due to a short amino terminal sequence which is subject to palmitoylation. Binding to actin filaments may also assist in restricting the protein to specific cellular domains. Consistent with its role as a "plasticity protein," there is evidence that GAP-43 can directly alter cell shape and neurite extension, and several theses have been advanced for how it might do so. Two other prominent components of the growth cone membrane are the alpha and beta subunits of G0. GAP-43 regulates their guanine nucleotide exchange, which is an unusual role for an intracellular protein. We speculate that GAP-43 may adjust the "set point" of responsiveness for G0 stimulation by receptors, thereby altering the neuronal propensity to growth, without actually causing growth. To begin to address how G protein activity affects axon growth, we have developed a means to introduce guanine nucleotide analogs into sympathetic neurons. Stimulation of G proteins with GTP-gamma-S retards axon growth, whereas GDP-beta-S enhances it. This is compatible with G protein registration of inhibitory signals.
Strittmatter
S M
SM
Department of Neurology, Massachusetts General Hospital-East, Charlestown 02129.
Vartanian
T
T
Fishman
M C
MC
D000199:Actins / Q000378:metabolism; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D019922:GAP-43 Protein; D019204:GTP-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009473:Neuronal Plasticity; D015398:Signal Transduction
D000199:Actins; D015816:Cell Adhesion Molecules, Neuronal; D019922:GAP-43 Protein; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019204:GTP-Binding Proteins