| Annotated protein: | Phosphatase and actin regulator 1. Gene symbol: PHACTR1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: P62024 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ PHACTR1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of modification of postsynaptic structure (GO:0099159) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Fedoryshchak RO, et al. "Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme" Elife. 2020 Sep 25;9:e61509 PMID:32975518 |
| Figure(s): | Figure 3 suppl. 2 |
| Annotation description: | "The cytoskeletal regulator Phactr1 is a neuronally enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating a new composite surface adjacent to the catalytic site." Authors identify substrates for Phactr1/PP1 (to be dephosphorylated), their specificities and elucidate the 3D structures for respective complexes. Specifically for synapses; rat hippocampal neurons that were transfected with plasmids overexpressing Phactr1 mutants exhibited abnormal dendritic spine morphology (Figure 3, supplement 2). The overexpressed Phactr1XXX is an activated Phactr1 derivative that constitutively forms the Phactr1/PP1 complex and induces F-actin rearrangements in NIH3T3 fibroblasts (Wiezlak et al., 2012. PMID:22976292). Authors discuss: "We identified multiple Phactr1-dependent substrates in hippocampal neurons. Several of these, including IRSp53 and spectrin αII, are dephosphorylated during long-term potentiation (LTP) (Li et al., 2016), and IRSp53-null mice exhibit deficits in hippocampal learning and memory (Bobsin and Kreienkamp, 2016; Kang et al., 2016). Moreover, dephosphorylation of cofilin is implicated in early-stage dendritic spine remodelling, along with G-actin itself (Bosch et al., 2014; Lei et al., 2017). These data suggest that rho-actin signalling to Phactr1 and the resulting protein dephosphorylations may contribute to synaptic plasticity, and indeed in humans Phactr1 mutations cause the infantile seizure condition West syndrome (Hamada et al., 2018). There may be multiple targets for rho-actin signalling to RPEL proteins in this setting, as the RPEL protein ArhGAP12 (Diring et al., 2019) also influences dendritic spine morphology (Ba et al., 2016). Future work will focus on the functional significance of neuronal rho-actin signalling to Phactr/PP1 substrates." |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | Over-expression |
| Evidence tracking, Experiment Assay: | Confocal |
| 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 |
| SynGO annotation ID: | 5412 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |