| Annotated protein: | Syntaxin-binding protein 5 (Lethal(2) giant larvae protein homolog 3) (Tomosyn-1). Gene symbol: STXBP5. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q8K400 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ STXBP5 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synaptic vesicle priming (GO:0010807) |
| Synapse type(s): | hippocampus superior cervical ganglion (SCG) Mossy fiber synapse (DG->CA3) |
| Annotated paper: | Sakisaka T, et al. "Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release" J Cell Biol. 2008 Oct 20;183(2):323-37 PMID:18936251 |
| Figure(s): | Fig. 1, Fig. 2A, Fig. 3 A, B; Fig. 4 C, D; Fig. 5 B, C, Fig. 7 |
| Annotation description: | In this study, by studying acetylcholine release in tomosyn-1 deficient mice, Sakisaka et al show that besides the inhibitory role of the VAMP-like domain in the C-terminus of tomosyn, the N-terminal WD40 repeat domain catalyzes oligomerization of SNARE complexes and thus provides an additional level of negative regulation of exocytosis. After verifying the Tom1 KO by Western blot (Fig. 1), the authors measured EPSCs at hippocampal mossy fiber synapses and found enhanced synaptic activity in the Tom1 KO (fig. 1D). Short-term plasticity (PPF) revealed increased release probability in KO (fig. 1E) mice. Moreover, LTP was affected, but only in the first phase (fig. 1F and G). Thus, the authors suggested that tomosyn-1 exhibits an inhibitory role at synapses in vivo. Addition of MBP-tomosyn 1 to brain extracts from KO mice restored the formation of oligomerized SNARE complexes (Fig. 2A). in a dose-dependent manner (fig. 3 A and B). By using an in vtiro assay, Sakisaka et al showed that syntaxin 1 and SNAP25 bind tom1 even if it is lacking the C-terminal VAMP-like domain (VLD, MBP-tomosyn-dVLD) and that the presence of VAMP2 in the mixture decreased the binding of the other two SNARE proteins to tom1 and induced the formation of SNARE complex oligomers (fig. 4 C and D). To support these observations, the authors demonstrated that tomosyn1-dVLD enhanced stronger than full lenght tomosyn1 the formation of SNARE compelx oligomers in a dose-dependent manner (Fig. 5 B and C). In fig. 7 A-C, the authors showed that the WD40 domain containing C-terminal part of tomosyn 1 is resposnible for the oligomerization of SNARE complexes.Microinjection of the mentioned expressed protein fragments in cultured SCG neurons induced reduction of EPSCs, suggesting that the SNARE complex oligomerization inhibits NT release. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Cell-free system |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection) |
| Evidence tracking, Experiment Assay: | Electrophysiology (generic) Western blot |
| 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 |
| SynGO annotation ID: | 2606 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |