| Annotated protein: | PRKCA-binding protein (Protein interacting with C kinase 1) (Protein kinase C-alpha-binding protein). Gene symbol: PICK1. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9EP80 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ PICK1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Fiuza M, et al. "PICK1 regulates AMPA receptor endocytosis via direct interactions with AP2 alpha-appendage and dynamin" J Cell Biol. 2017 Oct 2;216(10):3323-3338 PMID:28855251 |
| Figure(s): | Fig.6, 7 |
| Annotation description: | Fig.6: "PICK1 is required for clustering AMPARs at EZs via competitive binding of GluA2 and AP2" - " Under basal conditions, we detected a proportion of surface GluA2 puncta colocalizing with dsRed-clathrin clusters, which was significantly increased 2 min after NMDAR stimulation, strongly suggesting a recruitment of GluA2-containing AMPARs to CCPs (Fig. 6 B). At 2 min after stimulation, AMPARs had not yet internalized. This was blocked by PICK1 shRNA, indicating that PICK1 is required for this process." Fig.7: "PICK1-AP2 interaction is required for AMPAR endocytosis after NMDAR activation" - "Under basal conditions, PICK1 knockdown caused an increase in surface GluA2, consistent with previous studies (Sossa et al., 2006; Citri et al., 2010; Rocca et al., 2013). Sh-resistant WT-PICK1 fully rescued surface GluA2 levels, but D189A-PICK1 did not (Fig. 7 A). This indicates that the interaction between PICK1 and AP2 is required for constitutive AMPAR endocytosis" - "In GFP-expressing control neurons, NMDA caused a significant decrease in surface GluA2, which was blocked by PICK1 shRNA (Fig. 7 B). Whereas sh-resistant WT-PICK1 rescued the phenotype, DDAA-PICK1 did not, indicating that PICK1-AP2 interactions are required for NMDA-stimulated AMPAR internalization. " - "neither PICK1 knockdown nor molecular replacement with DDAA-PICK1 affected transferrin uptake, indicating that PICK1 is not involved in transferrin receptor endocytosis" |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Confocal Western blot |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) 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: | 2917 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |