| Annotated protein: | Adhesion G protein-coupled receptor L3 (Latrophilin-3) (Lectomedin-3). Gene symbol: ADGRL3. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q80TS3 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ ADGRL3 |
| Ontology domain: | Biological Process |
| SynGO term: | synapse assembly (GO:0007416) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Sando R, et al. "Latrophilin GPCRs direct synapse specificity by coincident binding of FLRTs and teneurins" Science. 2019 Feb 22;363(6429):eaav7969 PMID:30792275 |
| Figure(s): | Fig. 1c-i; Fig. 2c,d; Fig. 4; Fig. 5c,d; Fig. 6b,c,d; Fig. 7; Fig. S9a-c |
| Annotation description: | The authors describe the function of Latrophilin-3 in Schaffer collateral synapses in CA1 neurons using a Latrophilin-3 knockout (KO) mice. In KO mice, reductions were found in vitro in excitatory synapse density and mEPSC frequency (but not inhibitory synapse density or mIPSCs) in hippocampal cultured neurons (Fig. 1c-i; Fig. 2c, d) and in vivo in spine density of CA1 neurons in Stratum oriens and S. radiatum, but not S. lacunosum-moleculare (which expresses Latrophilin-2) of hippocampal slices (Fig. 4c-e). In accordance, mEPSC frequency and Schaffer Collateral AMPAR-specific EPSCs (but not mIPSC or Perforant Path AMPAR-specific EPSCs) were reduced (Fig 4f-m). Then the authors describe that Latrophilin-3 requires simultaneous binding with FLRT3 and teneurin-2 for its function. Reduced spine density in vitro, and reduced mEPSC frequency and AMPAR EPSCs were rescued in vitro (Fig. 2c,d) and in vivo (Fig. 5c,d) using overexpression of WT Latrophilin-3 or a mutant with abolished autoproteolysis, but not of mutants with abolished FLRT (Latrophilin-3 with mutant Olfactomedin-like domain) or teneurin (Latrophilin-3 mutant without Lectin-like domain) interaction. WT Latrophilin-3, with its FLRT and teneurin interaction domains, was necessary for maintaining synapse formation of ipsi- and contralateral Schaffer-collateral synapses (Fig. 6b,c,d). Lastly, the authors show that teneurin-2 and FLRT3 elicit post-synapse formation in co-cultured neurons only when expressed together in HEK293T cells (Fig. 7). Latrophilin-3 in HEK293T cells induces presynaptic excitatory specialization in co-cultured neurons (Fig. S9a-c). |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp Electrophysiology (generic) |
| Annotator(s): | Tony Cijsouw (ORCID:0000-0003-0912-1514) Thomas Biederer (ORCID:0000-0002-3670-7863) |
| Lab: | Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA |
| SynGO annotation ID: | 3978 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |