Role of tetanus neurotoxin insensitive vesicle-associated membrane protein (TI-VAMP) in vesicular transport mediating neurite outgrowth.
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 NH(2)-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 NH(2)-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 NH(2)-terminal domain as a key regulator in this process.
Martinez-Arca
S
S
Group of Membrane Traffic and Neuronal Plasticity, INSERM U536, Paris, France.
Alberts
P
P
Zahraoui
A
A
Louvard
D
D
Galli
T
T
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001905:Botulinum Toxins / Q000494:pharmacology; D002454:Cell Differentiation; D005089:Exocytosis / Q000187:drug effects; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites; D009474:Neurons / Q000166:cytology*; D016716:PC12 Cells; D011485:Protein Binding; D050683:R-SNARE Proteins; D051381:Rats; D050600:SNARE Proteins; D019311:Staurosporine / Q000494:pharmacology; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin / Q000494:pharmacology; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D013744:Tetanus Toxin; C496926:Vamp7 protein, rat; D033921:Vesicular Transport Proteins; C035979:tetanospasmin; D008666:Metalloendopeptidases; D001905:Botulinum Toxins; D019311:Staurosporine; C096326:botulinum toxin type E