| 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): | hippocampus cerebellum |
| Annotated paper: | Nicholson-Fish JC, et al. "VAMP4 Is an Essential Cargo Molecule for Activity-Dependent Bulk Endocytosis" Neuron. 2015 Dec 2;88(5):973-984 PMID:26607000 |
| Figure(s): | Fig 6-8 |
| Annotation description: | Activity-dependent bulk endocytosis (ADBE) is the dominant SV endocytosis mode under intense neuronal activity. The authors investigated whether directed sorting of SV cargo occurs at the plasma membrane during ADBE, since this will ultimately impact on the molecular composition of SVs generated via this endocytosis mode. They examined the retrieval of different SV cargo molecules during intense stimulation using a series of genetically encoded pH-sensitive reporters in neuronal cultures, and they found that only one was preferentially trafficked via ADBE-VAMP4. Author showed two important results: 1) VAMP4 is not simply represented as an ADBE cargo, actually authors showed by using biochemical fractionation experiments, that endogenous VAMP4 was selectively enriched on bulk endosomes. 2) VAMP4 is essential for ADBE to proceed. Authors determined this by using validated shRNA oligonucleotides against VAMP4. When 40Hz/10s stimulation was applied, VAMP4 knockdown abolished TMR-dextran uptake, an inhibition fully rescued by expression of wild-type VAMP4- pHluorin (Figures 7B and C). Therefore, in addition to being the first identified ADBE cargo molecule, VAMP4 is essential for this key endocytosis mode. VAMP4 Location: Figure 7A --> Representative images show nerve terminals labeled with VAMP4 antibodies after immunogold detection and silver enhancement. Almost all silver particles were localized to endosomal structures after 40 Hz stimulation (indicated by arrows). |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) RNAi / shRNA Antibody (detection) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Wide-field fluorescence Optical physiology Western blot Biochemical fractionation (generic) |
| Annotator(s): | Ryan J. Farrell (ORCID:0000-0003-4022-8707) Ghazaleh Ashrafi (ORCID:0000-0001-7480-0826) Camila Pulido (ORCID:0000-0002-5648-066X) Jaime de Juan-Sanz (ORCID:0000-0002-1212-5623) Timothy Ryan (ORCID:0000-0003-2533-9548) |
| Lab: | Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA |
| SynGO annotation ID: | 320 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |