| Annotated protein: | Copine-6 (Copine VI) (Neuronal-copine) (N-copine). Gene symbol: CPNE6. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9Z140 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CPNE6 |
| Ontology domain: | Biological Process |
| SynGO term: | postsynaptic actin cytoskeleton organization (GO:0098974) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Reinhard JR, et al. "The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory" Nat Commun. 2016 May 19;7:11613 PMID:27194588 |
| Figure(s): | Figure 5, 6 and Supplementary figure 8 and 9 |
| Annotation description: | Rac1 is part of the Rac1-PAK-LIMK1-Cofilin signalling pathway that is crucial for actin reorganisation in the postsynapse. To test whether CPNE6 regulates this pathway, co-expression experiments were carried out. Figure 5a and b: CPNE6 coimmunoprecipitates with RAC1 derived from Cos7 and hippocampal neuron lysates. Figure 5e: Co-expression of CPNE6 resulted in a strong increase in the total amount of active Rac1-GTP Figure S8c: CPNE6 recruits RAC1-PAK complex to the plasma membrane and activates Rac1 in cos7 cells. Figure S9a: Cofilin was not significantly increased in spines of Cpne6 KO neurons on cLTP indicating defective Rac1-PAK-LIMK1-Cofilin signalling. Figure S9b: Phosphorylation of Cofilin was reduced in CPNE6 hippocampal cultures compared to WT. Figure 6d: Extracellular field potential recordings of hippocampal slices show a reduction in fEPSP slope compared to WT. This effect was neutralised with the addition of jasplakinolide (a toxin that stabilised newly formed actin filaments) further solidifying the role of cpne6 in the stabilisation of subsynaptic actin cytoskeleton. The 'regulates' box was ticked because CPNE6 was shown to phosphorylate Cofilin (Figure S9b) and regulate the Rac1-PAK-LIMK1-Cofilin signalling pathway required for actin organisation. |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Antagonist / agonist Antibody (detection) |
| Evidence tracking, Experiment Assay: | Wide-field fluorescence Field recordings Biochemical fractionation (generic) |
| Annotator(s): | Dnyanada Sahasrabudhe (ORCID:0000-0003-2916-7616) 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: | 4005 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |