| Annotated protein: | Endophilin-A1 (Endophilin-1) (SH3 domain protein 2A) (SH3 domain-containing GRB2-like protein 2) (SH3p4). Gene symbol: SH3GL2. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: O35179 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ SH3GL2 |
| Ontology domain: | Biological Process |
| SynGO term: | synaptic vesicle endocytosis (GO:0048488) |
| Synapse type(s): | neocortex |
| Annotated paper: | Milosevic I, et al. "Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission" Neuron. 2011 Nov 17;72(4):587-601 PMID:22099461 |
| Figure(s): | fig 4, fig 5 |
| Annotation description: | The authors generate triple knockout (KO) mice for mouse endophilin 1, 2 and 3. One problem with this paper is that while it CLEARLY demonstrates a vital role for endophilins in synaptic vesicle (SV) recycling, it remains somewhat unclear as to which endophilin isoform is required. In fig 4, the authors generate cortical neuron cultures from endophilin 1/2/3 triple KO mice. They use synaptopHlourin (both the synaptophysin or vGLUT forms) to monitor SV endocytosis. Following a 10Hz for 30 sec stimulus (300 action potentials) the rate of SV recovery by endocytosis is measured. The triple KO mice show a significant decrease in endocytosis. Importantly, fig 4B/D/E show that this phenotype can be rescues by full-length endophilin 1. In fig 5 the authors use EM in mouse cortical cultures to demonstrate that the endophilin triple KO mice have a massive accumulation of clathrin-coated vesicles (CCVs). This demonstrates that endophilins are required for uncoating CCVs but not for their formation or fission, but does not distinguish between endophilin isoforms. 19/6/2017 Pim - The role of endophilin 1 is shown by the rescue of the tripple KO phenotype by over-expression of rat endophilin 1. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression |
| Evidence tracking, Experiment Assay: | Electron Microscopy Optical physiology |
| Annotator(s): | Peter McPherson (ORCID:0000-0001-7806-5662) |
| Lab: | Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada |
| Additional literature: | The authors use rat hippocampal neurons that they transfect with siRNA to knockdown endophilin 1. In fig 3 they use electrophysiology to stimulate the neuron with 100 pulses at 5 Hz. Endophilin 1 knockdown causes a decrease in the normalized amplitude of response (indicating a synaptic depression due to decreased SV recycling). @ PMID:26682072 |
| SynGO annotation ID: | 666 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |