Role of Tetanus Neurotoxin Insensitive Vesicle-associated Membrane Protein (TI-VAMP) in Vesicular Transport Mediating Neurite Outgrowth

doi:10.1083/jcb.149.4.889

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© The Rockefeller University Press, 0021-9525/2000/5/889/ $5.00
The Journal of Cell Biology, Volume 149, Number 4, May 15, 2000 889-900

Original Article

Role of Tetanus Neurotoxin Insensitive Vesicle-associated Membrane Protein (TI-VAMP) in Vesicular Transport Mediating Neurite Outgrowth

Sonia Martinez-Arca^a,b, Philipp Alberts^a,b, Ahmed Zahraoui^b, Daniel Louvard^b, and Thierry Galli^a,b
^a Group of Membrane Traffic and Neuronal Plasticity, INSERM U536
^b Group of Morphogenesis and Cell Signaling, CNRS UMR144, Institut Curie, F-75005 Paris, France

Correspondence to: Thierry Galli, INSERM U536 and CNRS UMR144, Institut Curie, Section de Recherche, 26 rue d'Ulm, 75231 Paris Cédex 05, France. Tel:33 142 346 372 Fax:33 142 346 377 E-mail:thierry.galli{at}curie.fr.

How vesicular transport participates in neurite outgrowth isstill poorly understood. Neurite outgrowth is not sensitiveto tetanus neurotoxin thus does not involve synaptobrevin-mediatedvesicular transport to the plasma membrane of neurons. Tetanusneurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP)is a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusionprotein [NSF] attachment protein [SNAP] receptor), involvedin transport to the apical plasma membrane in epithelial cells,a tetanus neurotoxin-resistant pathway. Here we show that TI-VAMPis essential for vesicular transport-mediating neurite outgrowthin staurosporine-differentiated PC12 cells. The NH₂-terminaldomain, which precedes the SNARE motif of TI-VAMP, inhibitsthe association of TI-VAMP with synaptosome-associated proteinof 25 kD (SNAP25). Expression of this domain inhibits neuriteoutgrowth as potently as Botulinum neurotoxin E, which cleavesSNAP25. In contrast, expression of the NH₂-terminal deletionmutant of TI-VAMP increases SNARE complex formation and stronglystimulates neurite outgrowth. These results provide the firstfunctional evidence for the role of TI-VAMP in neurite outgrowthand point to its NH₂-terminal domain as a key regulator in thisprocess.

Key Words: membrane traffic, neurite outgrowth, SNAREs, TI-VAMP, SNAP25

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