| Annotated protein: | AP-3 complex subunit delta-1 (AP-3 complex subunit delta) (Adaptor-related protein complex 3 subunit delta-1) (Delta-adaptin) (mBLVR1). Gene symbol: AP3D1. Taxonomy: Mus musculus (Mouse). Uniprot ID: O54774 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ AP3D1 |
| Ontology domain: | Biological Process |
| SynGO term: | neurotransmitter receptor transport, postsynaptic endosome to lysosome (GO:0098943) |
| 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): | Fig.5, S5, 6, S12, 7 |
| Annotation description: | Background: paper shows that stargazin regulates AMPAR trafficking via differential interactions with AP-2 and AP-3 depending on the phosphorylation state of stargazin. The interaction of stargazin with both AP-3 and AP-2 seems to be needed for NMDA-induced AMPA receptor endocytosis, a chemical LTD model, in hippocampal neurons. This is unexpected since only AP-2 complex is known to be involved in clathrin-mediated endocytosis. In further experiments the authors show that it is not the endocytosis that is regulated by AP-3, but the targeting to the lysosomal compartment; if AP-3 function is perturbed the AMPARs are no longer degraded, but travel back to the plasma membrane preventing a run-down of the cell surface receptor levels. Fig 5-S5: "Knockdown of AP-2 or AP-3A inhibits the NMDA-induced removal of surface AMPA receptors" Fig.6: "Binding of STG to AP-3A is required to prevent recycling of GluA2 to the cell surface." Fig. S12 demonstrates that siRNA for AP-3 delta reduces the co-localization of GluA2 with lysosomal markers following GluA2 endocytosis induced by NMDA. Fig.S12: Literal: "These results indicate that the AMPA receptors endocytosed during NMDA-induced LTD are at least partially degraded via AP-3-dependent trafficking to lysosomes." Fig.7: "Suppression of hippocampal CA1-LTD by inhibiting the interaction of STG with AP-2 or AP-3A" This figure supports the relevance of the AP-2 role in in vivo synapses (AP-2 function is perturbed indirectly). Note: the paper mentions shRNA against AP-3 delta subunit. This is traced back to AP-3 delta1 via blast using the shRNA sequences (GUG AGA AGC UGC CUG UCC A). |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Wide-field fluorescence Western blot |
| 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 |
| SynGO annotation ID: | 2226 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |