| Annotated protein: | Contactin-associated protein-like 4 (Cell recognition molecule Caspr4). Gene symbol: CNTNAP4. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q99P47 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CNTNAP4 |
| Ontology domain: | Biological Process |
| SynGO term: | modulation of chemical synaptic transmission (GO:0050804) |
| Synapse type(s): | cerebral cortex, GABAergic |
| Annotated paper: | Karayannis T, et al. "Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission" Nature. 2014 Jul 10;511(7508):236-40 PMID:24870235 |
| Figure(s): | Figure 2, Figure 3, Extended Data Fig. 2b-c, Extended Data Fig. 3a and Extended Data Fig. 5 |
| Annotation description: | Figure 2, Extended Data Fig. 2b-c, Extended Data Fig. 3a: Cntnap4 mutant mice show increased dopamine but decreased GABA signalling. Literal: "We used fast-scan cyclic voltammetry to monitor axonal dopamine spillover in the caudate putamen (CPu) and nucleus accumbens (NAc) of heterozygous, knockout and wild-type mice11. Dopamine release was evoked by single or brief pulse trains (20 pulses at 10 Hz or 5 pulses at varying frequencies). Both heterozygous and knockout mice compared to wild-type animals, showed an increase in peak extracellular dopamine concentration ([DA]o) that was more pronounced in the NAc than CPu, especially with multiple pulse stimulation (Fig. 2a)." "However, in Cntnap4 knockout animals compared to controls, spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal cells were fewer, smaller and slower (Extended Data Fig. 2b). Intriguingly, paired-cell recordings between PV and excitatory cells in three-week-old knockout mice had synaptic responses reminiscent of those in immature fast spiking (FS) cells13 (Fig. 2b). IPSC amplitude was reduced and kinetics were prolonged, with longer rise-times and decay tau values (Fig. 2b, c and Extended Data Fig. 2c). In addition, the average latency of the IPSCs was marginally increased and between-trials variability (jitter) was larger (Fig. 2b, c). Some of these defects persisted into adulthood and hence were not due to developmental delay (Extended Data Fig. 3a). By comparing Cntnap4-positive and Cntnap4-negative PV interneurons at P21 (Fig. 2c) we observed that negative cells resembled mutant neurons. This indicates not only that the defects we saw are cell-autonomous (Cntnap4-negative PV-positive interneurons, grey symbols versus Cntnap4 knockout cells, red symbols, Fig. 2c), but also that Cntnap4 appears necessary for the full maturation of the output of PV-positive interneurons." Figure 3 and Extended Data Fig. 5: Loss of Cntnap4 results in ultrastructural deficits in perisomatic inhibitory synapses. Literal: "we examined symmetric perisomatic synapses onto pyramidal cells by electron microscopy (EM) in adult knockout, heterozygous and wild-type animals (Fig. 3a). We observed that the cleft width was significantly larger in the heterozygotes versus wild types, and was further increased in the knockout mice (wild type, 14.37±0.28nm; heterozygote, 15.61±0.28 nm; knockout, 17.37±0.43 nm) (Fig. 3a, b), whereas the postsynaptic density (PSD) was shortest in the knockout and intermediate in heterozygotes compared to wild-type mice (Fig. 3a, b) (wild-type, 221.71±7.34 nm, heterozygote, 195.45±6.9 nm, knockout, 185.34±6.67 nm). By contrast, excitatory (compared to inhibitory) synapses exhibited a significant butmilder widening of the synaptic cleft in knockout versus wild-typemice (6.4% versus a 20.8% increase; Extended Data Fig. 5) and no difference in excitatory PSD length. Our results show that Cntnap4 joins the short list of molecules that contribute to the structural maturation of inhibitory interneuron synapses and acts in a gene dose-dependent manner." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Electrophysiology (generic) |
| Annotator(s): | Chiara Verpelli (ORCID:0000-0003-2949-9725) Carlo Sala (ORCID:0000-0003-0662-9523) |
| Lab: | CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy |
| SynGO annotation ID: | 3678 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |