| Annotated protein: | Lethal giant larvae homologue 2 domain-containing protein (Tomosyn isoform A). Gene symbol: TOM-1. Taxonomy: Caenorhabditis elegans (Worm). Uniprot ID: Q49HI3 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ STXBP5 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of synaptic vesicle priming (GO:0010807) |
| Annotated paper: | McEwen JM, et al. "Antagonistic regulation of synaptic vesicle priming by Tomosyn and UNC-13" Neuron. 2006 Aug 3;51(3):303-15 PMID:16880125 |
| Figure(s): | Fig. 1 A-D, Fig 4 A,B |
| Annotation description: | In this paper, McEwen investigate the role of tomosyn-1 in C. elegans mutants lacking the protein (TOMO-1 mut). McEwen et al observe increased Ach secretion at tomo-1 mut body muscles by recording EPSCs. The authors find that stimulus-evoked EPSC amplitudes and total synaptic charge transfer are significantly increased in mutants (Fig. 1 A-D). This results suggest that tomosyn acts as inhibitor of synaptic transmission. In this line of experiments, by measuring of hypertonic sucrose evoked response, the authors show more than 400% increase in EPSC and total synaptic charge transfer, indicating that the increased secretion of Ach in tomo-1 mut is caused by increase in the pool of primed SVs (fig. 4A,B) These results are consistent with the reports mentioned in the additional literature, showing that overexpression of tomosyn in chromaffin cells reduces the number of primed vesicles (see Hatsuzawa 2003, Gracheva 2006 and Yizhar 2004). |
| Evidence tracking, Biological System: | Intact tissue Cell-free system |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression |
| Evidence tracking, Experiment Assay: | Wide-field fluorescence Whole-cell patch clamp unlisted assay type |
| 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: | The results from growth hormone release assay in PC12 cells suggest inhibition of exocytosis in PC12 cells by tomosyn-1, as shown by the authors for first time, however solid evidence is delivered by the findings in the primary reference. @ PMID:9620695 The authors of the study show that over-expression of the C-terminal domain of tomosyn-1 inhibits Ca-evoked exocytosis in a cell-free preparation from PC12 cells (as monitored by changes in fluorescence intensity of neuropeptide Y-EGFP-expressing PC12 cell-derived membrane sheets, Fig 5). In a second set of experiments, they perform carbon fiber amperometric measurements on tomosyn 1-expressing PC12 cells in order to investigate the frequency and release parameters of dopamine release and find that tomosyn-1 inhibits exocytosis by reducing the readiness of the secretory granules for exocytosis. @ PMID:12782620 Yizhar et al show that overexpression of tomosyn in adrenal chromaffin cells decreases the release probability and the number of primed vesicles. In order to achieve this, the authors overexpress tomosyn and investigate its effect on depolarization-induced secretion by membrane capacitance measurements. In comparison to control cells, secretory response is reduced upon tomosyn overexpression (Fig. 1a,b). In addition, Yizhar does not observe a change in calcium influx, but rather demonstrates reduction of release probability upon tomosyn expression (Fig 1d). By combination of capacitance measurements and flash photorelease of calcium, the authors report reduction of exocytotic burst (representing the fusion of release-competent vesicles) and enhancement of the sustained component after the burst (vesicle recruitment and subsequent fusion) (fig. 4 a,d,e) Further analysis of the fast and slow component of the exocytotic burst shows reduction of both compared to control cells (table 1). the data suggests inhibition of the vesicle priming into the RRP. @ PMID:14983051 The authors report investigation of the role of tomosyn-1 in C elegans in vivo in order to determine the protein's regulation mechanism on SV exocytosis. Electrophysiological analysis of tom-1 mut shows enhancement of EPSC and two fold increase in total synaptic charge transfer. In mutants, the number of membrane-bound SVs is increased, a phenotype that is reversed by tom-1 neuronal expression. Additionally, hyperosmotic responses in mutant worms indicate enhancement of primed vesicle pool (fig. 2,4 ,6) @ PMID:16895441 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, N-terminal WD40 repeat domain catalyzes oligomerization of SNARE complex and thus providing an additional level of negative regulation on exocytosis. @ PMID:18936251 Yu et al use in vitro fusion assays with purified proteins for recapitulation of tomosyn-regulated exocytosis. The authors report that tomosyn negatively regulates fusion by inhibiting assembly of ternary SNARE complex. Furthermore, Yu et al show that the effect is mediated not only by C-terminal domain of tomosyn containing the R-SNARE-like motif, but also by N terminal domain (critical but not sufficient for sytaxin 1 monomer binding). @ PMID:25063806 |
| SynGO annotation ID: | 1142 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |