| Annotated protein: | Syntaxin-3. Gene symbol: STX3. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q64704 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ STX3 |
| Ontology domain: | Biological Process |
| SynGO term: | exocytic insertion of neurotransmitter receptor to postsynaptic membrane (GO:0098967) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Jurado S, et al. "LTP requires a unique postsynaptic SNARE fusion machinery" Neuron. 2013 Feb 6;77(3):542-58 PMID:23395379 |
| Figure(s): | Fig. 1, 3, 5-7; Model in Fig. 8 |
| Annotation description: | As other SNARE molecules, syntaxin 3 is involved in fusion reaction between membranes. In this paper, the authors provide evidence for the participation of a SNARE fusion complex between Q-SNAREs syntaxin 3 and SNAP47, and R-SNARE VAMP2/synaptobrevin 2 in the exocytic delivery of AMPAR to postsynaptic membrane during LTP. Furthermore, Jurado et al show that syntaxin 3 is not important for the basal constitutive exocytosis of AMPAR. The authors use shRNA-mediated KD of proteins of interest combined with molecular displacement and rescue experiments. shRNAs are delivered into neurons in vitro and in vivo: for the in vivo experiments, after targeting the proteins in CA1 pyramidal cells, acute slices are prepared from those animals and whole cell patch clamp recordings are carried out. In contrast to previous reports, Jurado et al find that only syntaxin-3 KD (and not syntaxin 1 or 4) impairs glycine-induced increase in GluA1 surface expression (fig. 1K) and LTP in acute slices (fig. 1L). In addition, these results are inversed by shRNA-resistent full length syntaxin 3. However, rescue experiments fail upon loss of complexin binding site or N-terminal Munc18-binding sequence in syntaxin 3 (Fig. 3 A-C and fig. 3 J-L, respectively), emphasizing their importance. Furthermore, SNAP-47 KD is also shown not to affect basal constitutive, but only LTP-related AMPAR exocytosis and its function is dependent on the SNARE motif (fig. 5-6). In this line of experiments, by using VAMP-2 KO mice Jarudo can show that VAMP2 is, in contrast to SNAP-47 and Syntaxin 4, required for basal AMPAR exocytosis, but is indispensable only for NMDAR-mediated LTP-induced AMPAR exocytosis (fig. 7). Taken together, these results suggest that a SNARE fusion machinery composed of syntaxin 3, SNAP-47 and VAMP2 is required for NMDAR-mediated AMPAR exocytic insertion into postsynaptic membranes during LTP. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression Antagonist / agonist Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Microscopy (generic) Whole-cell patch clamp Electrophysiology (generic) Western blot Protein-protein interaction (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: | Peng et al investigate in detail the interaction of Munc18-2 with its cognate SNAREs stx3, VAMP8 and SNAP-23 (non-neuronal SNARE) and demonstrate by pulldown assays SNARE complex assembly between stx3, SNAP-23 and VAMP8 or VAMP2. (Fig. 2). @ PMID:20695848 The authors show by in vitro pulldown assays that phosphorylation of the regulatory protein Munc18b by CDK5 attenuates Munc18-2-syntaxin 3 interaction and promotes formation of stx3-SNAP25-VAMP2 complex (Fig. 3-4) @ PMID:17716669 Curtis et al show by RT-PCR (fig. 2) that syntaxin 3B is the preferentially expressed isoform of syntaxin 3 in retina and verify this finding by in situ hybridization in mouse retina sections (fig. 4). Furthermore, the authors perform for first time a reconstituted liposome fusion assay with syntaxin 3B/SNAP25 and VAMP2 liposomes and demonstrate that the three proteins can form a SNARE complex (Fig.8). Taken together, the results from all cited references suggest that syntaxin 3 can form complexes with SNAP-23 (non-neuronal cells)/SNAP25 and VAMP8/VAMP2. However, additional evidence for the existence of functional fusion complexes is required. @ PMID:18683220 |
| SynGO annotation ID: | 1182 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |