Annotated protein:E3 ubiquitin-protein ligase Rnf220 (EC 2.3.2.27) (RING finger protein 220) (RING-type E3 ubiquitin transferase Rnf220). Gene symbol: RNF220. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q6PDX6
antibody wiki:
SynGO gene info:SynGO data @ RNF220
Ontology domain:Biological Process
SynGO term:regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Ma P, et al. "RNF220 is an E3 ubiquitin ligase for AMPA receptors to regulate synaptic transmission" Sci Adv. 2022 Sep 30;8(39):eabq4736 PMID:36179027
Figure(s):Figures 2-7
Annotation description:Figure 2: RNF220 is present in synaptosomal, but not PSD, biochemical fractions prepared from hippocampal tissue. RNF220-knockout significantly affected relative abundance levels of GluA1 and 2 (GRIA1, GRIA2).

Figure 3: RNF220 regulates excitatory synaptic transmission and plasticity.
"We next examined the regulation of synaptic plasticity by RNF220 by inducing LTP (long-term potentiation) of the CA1 pyramidal neurons from RNF220 cKO mice and control littermates. It was shown that the potentiation of AMPAR-mediated EPSCs was significantly impaired in RNF220 depletion neurons (RNF220 KO, 239.69 ± 22.94% baseline; control, 442.02 ± 51.04% baseline; Fig. 3D). Together, all these data indicate that RNF220 regulates postsynaptic AMPAR expression to affect excitatory synaptic transmission and plasticity."

Figure 4: RNF220 directly ubiquitinates AMPARs to regulate excitatory synaptic activity.

Figure 5: "Together, these results indicate that RNF220 is an E3 ubiquitin ligase for AMPARs to control protein stability and regulate excitatory synaptic transmission."

Figure 6: RNF220 regulation of synaptic activity involves ubiquitination of both GluA1 and GluA2 receptors.

Figure 7: "Together, these results indicate that the ubiquitination regulatory mechanism by RNF220 is also involved in neuronal surface expression of AMPARs."

authors conclude:
"In this study, we find that RNF220 is an E3 ubiquitin ligase for AMPARs to repress their expression on neuronal surface and synapse."
Evidence tracking, Biological System:Intact tissue
Cultured neurons
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Antibody (detection)
Over-expression
Evidence tracking, Experiment Assay:Confocal
Western blot
Biochemical fractionation (generic)
IP + WB/MSMS
Whole-cell patch clamp
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:5234
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology