| Annotated protein: | Neurexin-3 (Neurexin III-alpha) (Neurexin-3-alpha). Gene symbol: NRXN3. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q6P9K9 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ NRXN3 |
| Ontology domain: | Biological Process |
| SynGO term: | trans-synaptic signaling, modulating synaptic transmission (GO:0099550) |
| Synapse type(s): | hippocampus, glutamatergic cerebellum, glutamatergic |
| Annotated paper: | Dai J, et al. "Distinct neurexin-cerebellin complexes control AMPA- and NMDA-receptor responses in a circuit-dependent manner" Elife. 2022 Oct 7;11:e78649 PMID:36205393 |
| Figure(s): | Figure 1-8 |
| Annotation description: | Nrxn1/3 - Cbln1/2 trans-synaptic signaling complexes differentially control NMDA- and AMPA-receptors in different synapses in diverse neural circuits without regulating synapse or spine formation. The Neurexin alternative splicing site 4 (SS4) is critical to these signaling pathways. Summary of paper figures; Figure 1: Constitutive Cbln2 deletion increases AMPAR-EPSCs and suppresses NMDAR-EPSCs at CA1→subiculum synapses formed on both burst- and regular-spiking subiculum neurons, and additionally blocks NMDAR-dependent LTP in regular-spiking neurons without affecting cAMP-dependent LTP in burst-spiking neurons. Figure 2: Constitutive Cbln2 deletion impairs contextual memory in the two-chamber avoidance test. Figure 3: Constitutive Cbln2 deletion does not alter the overall synapse density in the subiculum. Figure 4: Constitutive Cbln2 deletion occludes regulation of postsynaptic AMPAR- and NMDAR-EPSCs by presynaptic Nrxn1SS4+ and Nrxn3SS4+, respectively. Figure 5: Cbln1 and Cbln2 double KO in the subiculum phenocopies the Cbln2 single KO at CA1→subiculum synapses. Figure 6: Nrxn1SS4+ - Cbln2 signaling controls NMDAR-EPSCs but not AMPAR-EPSCs in the PFC, whereas Nrxn3SS4+-Cbln2 signaling does not regulate either AMPAR- or NMDAR-EPSCs in the PFC. Figure 7: Constitutive Cbln2 deletion does not alter the overall synapse density in the PFC. Figure 8: Nrxn3SS4+ - Cbln1 signaling controls AMPAR-EPSCs in the cerebellum, but in this brain region Nrxn1SS4+ - Cbln1 signaling has no effect. |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Electrophysiology (generic) Western blot |
| 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 |
| Additional literature: | "Here we show that at hippocampal synapses, NRXN1SS4+ and NRXN3SS4+ enhance NMDAR EPSCs and suppress AMPAR EPSCs, respectively, by activating GluD1 in a complex with CBLN2" @ PMID:34135511 |
| SynGO annotation ID: | 4995 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |