| Annotated protein: | MAGUK p55 subfamily member 2 (Discs large homolog 2) (Protein MPP2). Gene symbol: MPP2. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9WV34 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ MPP2 |
| Ontology domain: | Biological Process |
| SynGO term: | structural constituent of postsynaptic density (GO:0098919) |
| Synapse type(s): | Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Kim G, et al. "Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function" Elife. 2016 Feb 12;5:e12637 PMID:26880549 |
| Figure(s): | Fig. 1, 2, 4, 6, 7, 8 |
| Annotation description: | MPP2 is a synaptic MAGUK protein that localizes to the postsynaptic density of dendritic spines on CA1 pyramidal neurons. Fig. 1: "MPP2 interacts with SK2." Two different MPP2 antibodies (MPP2a, MPP2b were used for affinity-purification (AP) of MPP2 from membrane fractions isolated from adult rat brain tissue. Quantitative mass spectrometry found both antibodies purified MPP2 co-purified SK2 as well as SK3 (Fig. 1C, Supplementary file 1). Fig. 2: "MPP2 interacts with the N-terminal domain of SK2-L." This domain is required for synaptic localization of SK2-channels. C8-MPP2 specifically co-precipitated with both SK2 isoforms (SK2-L, SK2-S, HEK cells, Fig. 2A). GST pull-down experiments showed only the SH3-HOOK-GK domain from MPP2, but not SAP97 or CaCNB4, specifically pulled-down the N-terminal domain of SK2-L. Fig. 4: "MPP2 is required for synaptic SK2-containing channel function." Synaptically evoked EPSPs in control CA1 pyramidal neurons were potentiated by apamin, a SK channel blocker. EPSPs measured in MPP2-knockdown neurons were not significantly affected by apamin treatment. Fig. 6: "Co-expression of sh-immune MPP2 with MPP2 shRNA rescues synaptic SK2 function." Co-expression of shRNA-resistant MPP2 in knockdown neurons recovered apapmin-mediated potentiation of EPSPs similar to control neurons demonstrating restored SK2 channel function. Fig. 7: MPP2-knockdown selectively affected synaptic SK2-containing channel function. SK2-containing channels expressed in the dendrites that are activated by somatic voltage steps were unaffected. Fig. 8: "Loss of MPP2 reduces LTP." shRNA-knockdown of MPP2 reduced the expression of TBP-induced LTP by ~30% in CA1 neurons. This is slightly more than the component of LTP attributed to SK2 endocytosis in untransfected CA1 Fig. 5. Validation of MPP2-shRNA knockdown and specificity of MPP2 antibody using pre-embedding iEM was performed on hippocampal sections from MPP2 shRNA-transfected animals. MPP2 particles in spines and dendrites were significantly reduced in MPP2-knockdown neurons compared control, untransfected cells (81% and 78%, respectively). |
| Evidence tracking, Biological System: | Intact tissue Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Western blot IP + WB/MSMS Protein-protein interaction (generic) |
| Annotator(s): | Hana Goldschmidt (ORCID:0000-0002-5676-366X) Richard Huganir (ORCID:0000-0001-9783-5183) |
| Lab: | Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA and Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA |
| Additional literature: | Fig 1. "MPP2 is a component of postsynaptic receptor complexes." Immunoprecipitation of TARP γ-2 from crude synaptosomal fractions showed MPP2 is present in AMPAR complexes containing GluA2, PSD-95 and TARP γ-2 (Fig.2A). MPP2 localizes to excitatory synapses (Fig. 1B). Immunostaining of cultured hippocampal neurons showed endogenous MPP2 is exclusively found in neurons (MAP2 positive cells) and MPP2 puncta along dendrites colocalized with with PSD-95 and vGlut1. Fig. 2. MPP2 interacts with the postsynaptic density proteins PSD-95 and GKAP. The interaction between MPP2 with PSD-95 was demonstrated immunoprecipitation of endogenous MPP2 from crude synaptosomes isolated from adult rat brain tissue (Fig. 2B). In heterologous cells, MPP2 was capable of binding PSD-95 independent of its PDZ and L27 domains (Fig. 2A, 2C). @ PMID:27756895 |
| SynGO annotation ID: | 2585 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |