| Annotated protein: | Calcineurin subunit B type 1 (Protein phosphatase 2B regulatory subunit 1) (Protein phosphatase 3 regulatory subunit B alpha isoform 1). Gene symbol: PPP3R1. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q63810 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ PPP3R1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149) |
| Synapse type(s): | hippocampus, glutamatergic Schaffer collateral synapse (CA3->CA1) |
| Annotated paper: | Zeng H, et al. "Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory" Cell. 2001 Nov 30;107(5):617-29 PMID:11733061 |
| Figure(s): | Figure 3 |
| Annotation description: | A forebrain-specific knockout for calcineurin beta is created (CaNB is encoded by the gene PPP3R1, which is called CNB1 in this paper). This knockout has a strong reduction in LTD, as shown in figure 3. This process has been shown to be dependent on receptor endocytosis (Man et al 2000). In addition, pharmacological inhibition of calcineurin abolishes endocytosis of receptors (Beattie et al. 2004). 24/11/2017 Pim - Normally we would not allow annotation against the term 'postsynaptic neurotransmitter receptor endocytosis (GO:0098884)'. The reason is this may lead to very problematic/unintuitive gene-process annotations f.i. presynaptic proteins that affect LTP then also regulate postsynaptic NTR endocytosis. This is an exception to that guideline. There is functional data referenced (PMID:11100150, ticket #254) that shows that calcineurin is involved in NTR endocytosis, but this data does not distinguish between gene paralogs. Together with the data on LTP this makes the annotation against 'postsynaptic neurotransmitter receptor endocytosis (GO:0098884)' a straight-forward inference. This inference across mulitple papers is difficult to capture in a IC pattern. The authors themselves give two possible mechanisms that may underlie the LTP effect: "Two potential mechanisms by which calcineurin could trigger LTD have emerged from recent studies, both related to regulation of AMPA receptors. First, a recent study showed that LTD and dedepression are associated with the dephosphorylation and phosphorylation, respectively, of a PKA phosphorylation site on the GluR1 subunit of AMPA receptors ... A second possibility, not mutually exclusive with the first, is that calcineurin triggers LTD by stimulating AMPA receptor endocytosis (Beattie et al., 2000; Lin et al., 2000)." |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Field recordings |
| Annotator(s): | Arthur de Jong (ORCID:0000-0002-7620-2704) Pascal Kaeser (ORCID:0000-0002-1558-1958) |
| Lab: | Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA |
| Additional literature: | Man et.al. demonstrates that LTD requires endocytosis of receptors. @ PMID:10774732 Beattie et.al. shows that pharmacological inhibition of calcineurin abolishes AMPAR endocytosis. @ PMID:11100150 |
| SynGO annotation ID: | 255 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |