| Annotated protein: | Vesicle-associated membrane protein 4. Gene symbol: VAMP4. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: A0A096MJ99 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ VAMP4 |
| Ontology domain: | Biological Process |
| SynGO term: | synaptic vesicle to endosome fusion (GO:0016189) |
| Synapse type(s): | brain |
| Annotated paper: | Rizzoli SO, et al. "Evidence for early endosome-like fusion of recently endocytosed synaptic vesicles" Traffic. 2006 Sep;7(9):1163-76 PMID:17004320 |
| Figure(s): | Fig. 5 |
| Annotation description: | Fig. 5: In this study, Rizzoli et al show, using an in-vitro fusion assay, that the ATP-dependent fusion between neuronal endocytic vesicles and PC12-derived acceptor membranes is inhibited by recombinant endosomal proteins, such as syntaxin 6, syntaxin 13 and VAMP4. To further prove the specific involvement of endosomal SNAREs in the fusion reaction, the authors incubate neuronal and PC12 organelles with bacterial toxins (botulinum C1 and tetanus toxin), which cleave exocytotic SNAREs (synaptobrevin 2 and syntaxin 1, verified by Western blotting), but do not inhibit the reaction. Thus, the results suggest that syntaxin 6, syntaxin 13 and vamp4 are the endosomal SNAREs required for the fusion of SVs to early endosomes. |
| Evidence tracking, Biological System: | Intact tissue Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Over-expression |
| Evidence tracking, Experiment Assay: | Microscopy (generic) Optical physiology Biochemical fractionation (generic) |
| Annotator(s): | Momchil Ninov (ORCID:0000-0002-0808-7003) Mahdokht Kohansalnodehi (ORCID:0000-0002-3898-5197) Reinhard Jahn (ORCID:0000-0003-1542-3498) |
| Lab: | Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany |
| Additional literature: | Fig. 2, Fig 3: In this paper, the authors establish a new system in order to study the transport between early/recycling endosomes and TGN: Modified Shiga toxin B subunit (STxB) carries two COOH-terminal sites, which undergo sulfation (with [35]S radioactively labelled sulfate) by TGN-resident sulfotransferase. The sulfated STxB can be detected and quantified in streptolysin O-permeabilized HeLa cells. Addition of anti-syntaxin 6, syntaxin 16 and anti-vti1a antibodies to permeabilized HeLa cells blocks STxB translocation to TGN. Due to non-additive effect of STxB blockage by antibodies, the authors suggest involvement of all proteins in the same trafficking step and deliver suuporting information for interactions between the proteins by immunoprecipitation (IP). Also by IP, they identify Vamp3 and Vamp 4 as cognate SNARE partners and show the effect of their inhibition (by tetanus toxin cleaving specifically Vamp 3 in HeLa or by antibody blockage of STxB transport to TGN) on EE/RE -> TGN transport. In conclusion, Mallard, F. et al identify two syntaxin 6-containing SNARE complexes with syntaxin 16, Vti1a and VAMP3 or VAMP4 involved in retrograde trafficking. @ PMID:11839770 Fig. 1, Fig. S1: In this study, Hoopmann et al show direct involvement of the endosomal SNARE syntaxin 6 (as well as syntaxin-13 and vti1a) in synaptic vesicle recycling. The authors generate a reporter for syntaxin-6 (in addition to syntaxin-13 and vti1a) by linking it to pH-sensitive GFP (pHluorin). They show that upon fusion of SVs with presynaptic endosomes the GFP fluorescence (specific for each endosomal protein) is quenched (due to the low lumenal pH of the vesicles), whereas the signal increases upon exocytosis. Furthermore, the endosomal pHluorins are shown to recycle upon stimulationn train in hippocampal neurons causing fusion of RRP vesicles. Control syntaxin-1 pHluorin does not show involvement in vesicle cycling under the experimental conditions. Interestingly, Hoopmann et al demonstrate that the portion of cycling endosomal SNAREs participating in RRP exocytosis is similar to that of synaptopHluorin. Moreover, the authors show strong correlation between syt (labelled by intralumenal domain-recognizing fluorescent probe during exocytosis) and pHluorins of endosomal SNAREs in hippocampal culture. Thus, they provide additional support that syntaxin-6 (along with other endosomal SNAREs) is involved in the fusion of SVs with endosomal compartments during vesicle recycling. @ PMID:20956291 |
| SynGO annotation ID: | 2685 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |