| Annotated protein: | Adenylyl cyclase-associated protein 2 (CAP 2). Gene symbol: CAP2. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P52481 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CAP2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of modification of postsynaptic actin cytoskeleton (GO:1905274) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Pelucchi S, et al. "Cyclase-associated protein 2 dimerization regulates cofilin in synaptic plasticity and Alzheimer's disease" Brain Commun. 2020 Jun 26;2(2):fcaa086 PMID:33094279 |
| Figure(s): | Figure 3A-F, 6, 8A-D |
| Annotation description: | Figure 3A-C: analysis of the spine shape of hippocampal neurons transfected with CAP2-shRNA and GFP revealed a significant increase in spine length and head width. Figure 3D-F: Sholl analysis revealed a reduction in the complexity of the dendritic tree in hippocampal neurons transfected with CAP2-shRNA, as well as reduced total dendritic length. Collectively these data suggest that CAP2 is a protein relevant for shaping dendritic and spine morphology, which is deeply linked to the actin polymerization through cofilin activity. To investigate the direct effect of monomeric and dimeric CAP2 on the assembly and stability of individual actin filaments, authors employed in vitro dual-colour total internal reflection fluorescence microscopy. Figure 6A,B: actin depolymerization increases in the presence of CAP2. This was prevented by the mutation of Cys32 to glycine, which abolishes CAP2 dimerization. Figure 6C,D: analysis of the filaments showed that the CAP2-dependent increase in actin depolymerization rate was related to an increase in the severing activity. Figure 8A,B: the transfection of the shRNA-resistant CAP2 construct (shr-wt-CAP2), but not the expression of shr-C32G-CAP2, restores the LTP-driven translocation of cofilin to dendritic spines in primary hippocampal neurons. These data demonstrate that CAP2 and the Cys32-dependent dimerization of the protein are essential for the LTP-triggered cofilin trafficking to spines. Since cofilin translocation to spines during LTP is required for actin cytoskeleton dynamics and spine enlargement, authors verified whether the loss of Cys32 and, thereby, of CAP2 dimerization impairs LTP-induced spine remodelling. Figure 8C,D: cLTP induces the expected spine head enlargement in control conditions, but not in neurons transfected with CAP2-shRNA. The expression of the shr-wt-CAP2, but not of the mutant shr-C32G-CAP2, slightly potentiates the LTP-induced increase in spine head width. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Confocal Microscopy (generic) |
| Annotator(s): | Robin Clement Guus Smit Matthijs Verhage |
| ORCID: | 0000-0002-2286-1587 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: | 4893 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |