| Annotated protein: | Neurobeachin (Lysosomal-trafficking regulator 2). Gene symbol: NBEA. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9EPN1 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NBEA |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Gromova KV, et al. "Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior" Cell Rep. 2018 May 29;23(9):2705-2717 PMID:29847800 |
| Figure(s): | Fig.6 |
| Annotation description: | Fig.1; "Neurobeachin Is Located at Neuronal Dendrites and Synaptic Sites" - "NBEA displayed punctate distribution in dendrites (Figure 1A) ... NBEA signals were detected at spine synapses (Figure 1D)." Fig.2: "Neurobeachin Labels Nocodazole-Sensitive Tubules and Enters Active Spines in an Activity-Dependent Manner" - "Live imaging (5 min) under basal conditions revealed GFP-NBEA particle entry in 7.5% of observed spine heads (Figure 2G; mCherry: volume marker). Particle entry into spine protrusions was transient and lasted several seconds (Figure 2H). To verify that NBEA-positive spines indeed represent functional synapses, we performed a synaptotagmin antibody-uptake assay (Figure 2I). Interestingly, GFP-NBEA particles entered both active (40%) and inactive (60%) synapses (Figure 2I; Video S3). " Fig.4: " Neurobeachin Is Located to Tubular Structures Extending from Rab4-Positive Recycling Endosomes and Binds to Active Rab4" - " To determine a role for NBEA at Rab4 recycling endosomes (Stenmark, 2009), we used short hairpin RNA (shRNA)-based NBEA knockdown in N2a cells (Figures S4B and S4C) and assessed the speed and displacement of Rab4-positive particles. Converse to the GFP-NBEA overexpression findings (Video S4), NBEA knockdown increased the speed and distance of Rab4 vesicles (Figures 4I-4L), indicating a role for NBEA in regulating Rab4 endosome dynamics." Fig.6: "Neurobeachin Regulates Surface Membrane Recycling of GluN2B-Containing NMDA Receptors" - "Immunodetection revealed NBEA and GluN2B at spines opposed to synaptophysin-positive presynaptic terminals (Figure 5I), indicating colocalization at excitatory synapses." - "To assess whether NBEA regulates the recycling of GluN2B-containing NMDARs, we used a receptor-recycling assay based on cell surface biotinylation and co-streptavidin-precipitation in neurons derived from Nbea wild-type (+/+) and Nbea-knockout (-/-) mice (Figure 6G)." - "Although the total receptor content was similar for both genotypes (Figure 6B), we detected more than 50% reduction of GluN2B-NMDAR cell surface levels in NBEA-knockout neurons (Figures 6C and S6E-S6G). This corresponded with reduced NMDAR current amplitudes (Figures 6D-6F) and miniature excitatory postsynaptic current (mEPSC) frequencies (Figures S6B-S6D). " |
| Evidence tracking, Biological System: | Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) 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: | 3780 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |