title: The tetanus neurotoxin-sensitive and insensitive routes to and from the plasma membrane: fast and slow pathways?
abstract: Intracellular membrane trafficking in eukaryotes involves the budding of vesicles from a donor compartment, their translocation, and subsequent fusion with a target membrane. This last step has been shown to involve SNARE proteins, classified into two categories, vesicular (v)-SNAREs and target (t)-SNAREs. It is the pairing of v- and t-SNAREs that is responsible for bringing the lipid bilayers together for membrane fusion. Key to the discovery of SNAREs is the sensitivity of their neuronal synaptic prototypes, which mediate the release of neurotransmitters, to clostridial neurotoxins. In this review, we focus on tetanus neurotoxin-sensitive and tetanus neurotoxin-insensitive v-SNAREs, in particular synaptobrevin and cellubrevin, both tetanus neurotoxin-sensitive and Tetanus neurotoxin-Insensitive Vesicle-Associated Membrane Protein (TI-VAMP, also called VAMP7). The brevins are characterized by an RD sequence in the middle of their SNARE motif whereas TI-VAMP has an RG sequence. These two categories of exocytic v-SNAREs define two important routes to and from the plasma membrane: one sensitive, the other insensitive to tetanus neurotoxin. We also discuss the central role of the endosomal system that could be considered, as already suggested for Rab proteins, as a mosaic of v-SNAREs, thus raising the question of whether or not these two routes can merge, and if so, how and where.
authors.affiliation: Team 'Avenir' INSERM Membrane Traffic in Neuronal & Epithelial Morphogenesis Institut Jacques Monod CNRS/Univ. Paris 6/Univ. Paris 7 UMR7592, 2, place Jussieu, F-75251 Paris Cedex 05, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Proux-Gillardeaux
authors.forename: Rachel
authors.initials: R
authors.lastname: Rudge
authors.forename: Thierry
authors.initials: T
authors.lastname: Galli
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000494:pharmacology*; D008954:Models, Biological; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D015398:Signal Transduction; D013572:Synaptic Vesicles / Q000737:chemistry; D013744:Tetanus Toxin / Q000494:pharmacology*; D051040:Vesicle-Associated Membrane Protein 3; D033921:Vesicular Transport Proteins / Q000187:drug effects / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D013744:Tetanus Toxin; D051040:Vesicle-Associated Membrane Protein 3; D033921:Vesicular Transport Proteins; C035979:tetanospasmin; D008666:Metalloendopeptidases