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The Journal of Neuroscience, June 1, 2001, 21(11):3830-3838

A Common Exocytotic Mechanism Mediates Axonal and Dendritic Outgrowth

Sonia Martinez-Arca1, 4, Silvia Coco2, Gaëll Mainguy3, Ursula Schenk2, Philipp Alberts1, 4, Pascale Bouillé5, Mauro Mezzina5, Alain Prochiantz3, Michela Matteoli2, Daniel Louvard4, and Thierry Galli1, 4

1 Membrane Traffic and Neuronal Plasticity, Institut National de la Santé et de la Recherche Médicale U536, Institut du Fer-à-Moulin, F-75005 Paris, France, 2 Synaptic Development and Function, Cellular and Molecular Pharmacology and Bruno Ceccarelli Centers, Consiglio Nazionale delle Ricerche, 20129 Milan, Italy, 3 Developmental and Cellular Neurobiology, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8542, Ecole Normale Supérieure, F-75005 Paris, France, 4 Morphogenesis and Cell Signaling, CNRS UMR 144, Institut Curie, F-75005 Paris, France, and 5 Gene Therapy, Genethon III, Unité de Recherche Associée 1923, CNRS, BP 60, F-91002 Evry Cedex, France

Outgrowth of the dendrites and the axon is the basis of the establishment of the neuronal shape, and it requires addition of new membrane to both growing processes. It is not yet clear whether one or two exocytotic pathways are responsible for the respective outgrowth of axons and dendrites. We have previously shown that tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) defines a novel network of tubulovesicular structures present both at the leading edge of elongating dendrites and axons of immature hippocampal neurons developing in primary culture and that TI-VAMP is an essential protein for neurite outgrowth in PC12 cells. Here we show that the expression of the N-terminal domain of TI-VAMP inhibits the outgrowth of both dendrites and axons in neurons in primary culture. This effect is more prominent at the earliest stages of the development of neurons in vitro. Expression of the N-terminal domain deleted form of TI-VAMP has the opposite effect. This constitutively active form of TI-VAMP localizes as the endogenous protein, particularly concentrating at the leading edge of growing axons. Our results suggest that a common exocytotic mechanism that relies on TI-VAMP mediates both axonal and dendritic outgrowth in developing neurons.

Key words: axonal outgrowth; dendritic outgrowth; exocytosis; SNARE; TI-VAMP; adeno-associated virus; neurons in primary culture

Copyright © 2001 Society for Neuroscience  0270-6474/01/21113830-09$05.00/0


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