Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 475K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Martinez-Arca, S. Articles by Galli, T. Search for Related Content PubMed PubMed Citation Articles by Martinez-Arca, S. Articles by Galli, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Related Article Social Bookmarking                            What's this?

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

Role of Tetanus Neurotoxin Insensitive Vesicle-Associated Membrane Protein (Ti-Vamp) in Vesicular Transport Mediating Neurite Outgrowth

^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
INSERM U536 and CNRS UMR144, Institut Curie, Section de Recherche, 26 rue d'Ulm, 75231 Paris Cédex 05, France.33 142 346 37733 142 346 372

thierry.galli{at}curie.fr

How vesicular transport participates in neurite outgrowth is still poorly understood. Neurite outgrowth is not sensitive to tetanus neurotoxin thus does not involve synaptobrevin-mediated vesicular transport to the plasma membrane of neurons. Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] attachment protein [SNAP] receptor), involved in transport to the apical plasma membrane in epithelial cells, a tetanus neurotoxin-resistant pathway. Here we show that TI-VAMP is essential for vesicular transport-mediating neurite outgrowth in staurosporine-differentiated PC12 cells. The NH₂-terminal domain, which precedes the SNARE motif of TI-VAMP, inhibits the association of TI-VAMP with synaptosome-associated protein of 25 kD (SNAP25). Expression of this domain inhibits neurite outgrowth as potently as Botulinum neurotoxin E, which cleaves SNAP25. In contrast, expression of the NH₂-terminal deletion mutant of TI-VAMP increases SNARE complex formation and strongly stimulates neurite outgrowth. These results provide the first functional evidence for the role of TI-VAMP in neurite outgrowth and point to its NH₂-terminal domain as a key regulator in this process.

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

© 2000 The Rockefeller University Press

Abbreviations used in this paper: Nter-TIVAMP, NH₂-terminal domain-TIVAMP; BoNTs, Botulinum NTs; Cyt-TIVAMP, cytosolic domain-TIVAMP; GFP, green fluorescent protein; GFP-Cb, GFP-cellubrevin; GST, glutathione-S-transferase; LAMP1, lysosome-associated membrane protein 1; NSF, N-ethylmaleimide–sensitive fusion protein; NTs, neurotoxins; Nter-TIVAMP, NH₂-terminal domain-TIVAMP; SNAP, NSF attachment protein; SNARE, SNAP receptors; SVs, synaptic vesicles; TeNT, tetanus neurotoxin; TeNT-LC, TeNT light chain; TI-VAMP, TeNT-insensitive VAMP; t-SNARE, target SNARE; VAMP, vesicle-associated membrane protein; v-SNARE, vesicle SNARE.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents