| Annotated protein: | Ubiquitin carboxyl-terminal hydrolase CYLD (EC 3.4.19.12) (Deubiquitinating enzyme CYLD) (Ubiquitin thioesterase CYLD) (Ubiquitin-specific-processing protease CYLD). Gene symbol: CYLD. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q66H62 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CYLD |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Ma Q, et al. "Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity" Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8760-E8769 PMID:28973854 |
| Figure(s): | Figs. 8, 9 |
| Annotation description: | Traf6 is the E3 ubiquitin ligase that mediates constitutive K63 ubiquitination of PSD-95 (DLG4) (SynGO annotation #4898). Together with its deubiquitinase counterpart CYLD it controls PSD-95's clustering efficacy in spines and in turn controls cell surface availability of NMDA receptors in the postsynaptic membrane. "CYLD mediates NMDA-induced rapid PSD-95 declustering from spines" by deubiquitination of K63 (Fig. 8) upon CYLD knock down via shRNA (Panel E,F). "... K63-polyUb plays an essential role in synaptic maintenance and orderly organization of PSD-95 and LTD. PSD-95 is constitutively conjugated by K63-polyUb chains (by Ubc13/Uev1A-TRAF6), which maintains and compartmentalizes the protein (perhaps combined with other posttranslational modifications) to specific subdomains within the PSD. Synaptic activity opens NMDARs, allowing Ca2+ influx, and recruits/activates CYLD ..., which subsequently removes K63-polyUb from PSD-95." (Fig. 9) Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression (Fig. 9). |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Confocal Whole-cell patch clamp |
| Annotator(s): | Daniela Dieterich (ORCID:0000-0002-9880-1214) Rainer Pielot (ORCID:0000-0002-9681-3318) Karl-Heinz Smalla (ORCID:0000-0002-0269-0311) Eckart Gundelfinger (ORCID:0000-0001-9377-7414) |
| Lab: | Leibniz Institute for Neurobiology (LIN), Institute of Pharmacology and Toxicology, Otto von Guericke University, Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany |
| SynGO annotation ID: | 4535 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |