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Signal Transduction at the Neuronal Growth ConeNervous system development depends on axonal growth cone recognition of extracellular guidance clues and transduction of this information into directed growth. Major advances have been made in characterizing the extracellular molecules that serve as signals for growing axons, in correlating fluctuations of Ca,++ with motility, and in demonstrating the actin-dependent basis of growth cone motility. The intracellular events that immediately follow ligand-receptor interaction at the growth cone are largely undetermined. Molecules of the integrin family, the cadherin family, and the cell adhesion molecule family organize cytoskeletal changes directly but also may initiate signaling cascades involving diffusible messengers. Heterotrimeric G proteins are highly concentrated in the growth cone membrane and can account for the initial steps in signal transduction for several neurotransmitters that regulate axonal growth. GAP-43 enhances the sensitivity of G protein-mediated transduction. Molecules inhibitory for neuronal growth, such as collapsin, initiate a signal transduction cascade likely to involve G proteins and an intracellular protein, CRMP-62. Further analysis of growth cone signal transduction will provide a molecular understanding of the development of synaptic connectivity during brain development. The Neuroscientist 2:83-86, 1996
Key Words: KEY WORDS: Axonal growth cone • Growth cone collapse • Collapsin • Nervous system development • Nerve regeneration • GTP-binding proteins • CRMP-62 • GAP-43
The Neuroscientist, Vol. 2, No. 2,
83-86 (1996) |
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