| Annotated protein: | Ras-related protein Rab-4A (EC 3.6.5.2). Gene symbol: RAB4A. Taxonomy: Mus musculus (Mouse). Uniprot ID: P56371 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ RAB4A |
| Ontology domain: | Biological Process |
| SynGO term: | neurotransmitter receptor transport postsynaptic membrane to endosome (GO:0098968) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Matsuda S, et al. "Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression" Nat Commun. 2013;4:2759 PMID:24217640 |
| Figure(s): | Figure 6 |
| Annotation description: | Rab4 is an early endosome marker, Rab7 is a marker for late endosomes (Zerial and McBride, 2001. PMID:11252952). HA-GluA2 on the cell surface of living neurons was first labelled with an anti-HA antibody and NMDA was then applied to the neurons to induce HA-GluA2 endocytosis. The anti-HA antibody remaining on the cell surface was then removed by acid treatment; thus, the population of HA-GluA2 that was endocytosed by the NMDA treatment and recycled to the cell surface within 30 min could be specifically visualized. AP-3A generally mediates the transport of membrane proteins from early endosomes to late endosomes/lysosomes5. Thus, Stargazin/STG (gene=Cacng2) may regulate AMPA receptor trafficking to this pathway by binding to AP-3A. To test this hypothesis, we examined the location of STG following the NMDA treatment using an early endosome marker, Rab4, tagged with green fluorescent protein (GFP) and a late endosome/lysosome marker, Rab7, tagged with GFP, in hippocampal neurons. 3 min after NMDA treatment, STGwt and STGDAP3, but not STGDAP2, co-localized well with GFP-Rab4 (Fig. 6c,e), indicating that STGDAP2, which did not interact with AP-2 (Fig. 3a,b), was not endocytosed. By 10 min after the NMDA treatment, STGwt, STGDAP3 and STGDAP2 no longer co-localized with GFP-Rab4 (Fig. 6c,e); instead, STGwt started to co-localize with GFP-Rab7 but STGDAP3 and STGDAP2 did not (Fig. 6d,f). Authors conclude that Stargazin (Cacng2) has a critical role in regulating a trafficking pathway of AMPA receptors from the cell surface to early endosomes, here observed through labeling of GFP-Rab4 in hippocampal neurons. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Over-expression |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 4852 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |