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

Abstract

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.

The hyh mutation uncovers roles for αSnap in apical protein localization and control of neural cell fate

“…Localization and structure of the Golgi apparatus in embryonic neuroepithelial cells and adult neurons was normal as examined by electron microscopy or by GM130 immunostaining (data not shown). In contrast, the localization of Vamp7 (also known as TI-VAMP), a vesicle SNARE involved in apical membrane transport in epithelial cells 22,23 and neurons 24,25 , was strongly apical in normal neuroepithelial cells and profoundly disrupted in hyh mutants (Fig. 5k,l), suggesting that partial loss of αSnap disrupted its apical targeting function without disrupting all its cellular functions.…”

Myosin Vb controls biogenesis of post-Golgi Rab10 carriers during axon development

“…In line with this notion, the Golgi apparatus is associated with the sites of axon specification 55,56 . It seems that several types of vesicles provide the source of the membrane precursors 5,41,[57][58][59] . The possible interaction between these vesicular systems makes the dissection for the contribution of each system very difficult.…”

Syntaxin 7, syntaxin 8, Vti1 and VAMP7 (vesicle-associated membrane protein 7) form an active SNARE complex for early macropinocytic compartment fusion in Dictyostelium discoideum

“…In addition, it is worth mentioning that, in neuronal or PC12 cells, VAMP7 (TI-VAMP) localizes to a specialized tubulo-vesicular membrane compartment involved in neurite outgrowth [45]. This cell-specific VAMP7 activity corresponds to the formation of another SNARE complex involving SNAP-25 (synaptosome-associated protein of 25 kDa) [46]. Similarly, VAMP7 is involved in different vesicular transport processes, such as degranulation and apical delivery, possibly in a complex with SNAP-23 and syntaxin 3 [47,48].…”