Searle Scholar Profile : Pate Skene (1984)

Search: [ current | former scholar ] [ current | awarded institution ] [ quick search ]


	Pate Skene Associate Professor Department of Neurobiology Duke University Medical Center Box 3209 Durham, NC 27710 Voice: 919/681-6346 Fax: 919/681-4431 E-mail: skene@duke.edu Personal Homepage 1984 Searle Scholar

Regulation of Synaptic Plasticity

Assembly of synaptic circuits in a developing nervous system depends on the outgrowth of long axons, a process mediated by motile “growth cones” that form the advancing axon tips. As they mature, most neurons dramatically reduce expression of several genes encoding growth cone proteins. Dr. Skene's lab is interested in the molecular mechanisms by which the maturation of axons and their terminals leads to repression of neuronal genes, and in the consequences of this repression for synaptic plasticity and axon regeneration in adults. Using as a prototype the gene for a growth cone protein designated GAP-43, the lab is trying to identify cis-acting elements that render specific neuronal genes responsive to signals conveyed from intact axons to neuron cell bodies. Of special interest is a signaling pathway that appears to have undergone an important bifurcation in the course of vertebrate evolution, indicated by striking differences between amniotes (reptiles, birds, and mammals) and anamniotes (fishes and amphibians) in the responses of the GAP-43 gene to axon interruption in the central nervous system. A tight correlation between derepression of the GAP-43 gene and successful axon regeneration suggests that this gene responds to signaling pathways that control a neuron's ability to carry out effective axon elongation. A second line of investigation explores the dynamic post-translational fatty acylation of proteins in axon terminals, and the role of this reaction in axon growth and synaptic plasticity.