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Volume 17, Number 17, Issue of September 1, 1997 pp. 6575-6586
Copyright ©1997 Society for Neuroscience

Adenoviral Vector-Mediated Expression of B-50/GAP-43 Induces Alterations in the Membrane Organization of Olfactory Axon Terminals In Vivo

Received Jan. 23, 1997; revised June 12, 1997; accepted June 17, 1997.

Anthony J. G. D. Holtmaat1, 2, Wim T. J. M. C. Hermens1, 2, Marc A. F. Sonnemans1, Roman J. Giger1, Fred W. Van Leeuwen1, Michael G. Kaplitt3, A. Beate Oestreicher2, Willem Hendrik Gispen2, and Joost Verhaagen1, 2

1 Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam-ZO, The Netherlands, 2 Department of Medical Pharmacology, Rudolf Magnus Institute for Neuroscience, 3584 CJ Utrecht, The Netherlands, and 3 Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, New York 10021

B-50/GAP-43 is an intraneuronal membrane-associated growth cone protein with an important role in axonal growth and regeneration. By using adenoviral vector-directed expression of B-50/GAP-43 we studied the morphogenic action of B-50/GAP-43 in mature primary olfactory neurons that have established functional synaptic connections. B-50/GAP-43 induced gradual alterations in the morphology of olfactory synapses. In the first days after overexpression, small protrusions originating from the preterminal axon shaft and from the actual synaptic bouton were formed. With time the progressive formation of multiple ultraterminal branches resulted in axonal labyrinths composed of tightly packed sheaths of neuronal membrane. Thus, B-50/GAP-43 is a protein that can promote neuronal membrane expansion at synaptic boutons. This function of B-50/GAP-43 suggests that this protein may subserve an important role in ongoing structural synaptic plasticity in adult neurons and in neuronal membrane repair after injury to synaptic fields.

Key words: growth-associated protein B-50/GAP-43; adenoviral vector-mediated gene transfer; olfactory system; transgenic mice; axon morphology; synaptic plasticity




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