| 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 synaptic vesicle cycle (GO:0098693) |
| Synapse type(s): | cerebral cortex, glutamatergic hippocampus, glutamatergic Mossy fiber synapse (DG->CA3) |
| Annotated paper: | Cottrell JR, et al. "Working memory impairment in calcineurin knock-out mice is associated with alterations in synaptic vesicle cycling and disruption of high-frequency synaptic and network activity in prefrontal cortex" J Neurosci. 2013 Jul 3;33(27):10938-49 PMID:23825400 |
| Figure(s): | Figure 2 and 3 |
| Annotation description: | Cotrell et.al. demonstrated that PPP3R1 (Calcineurin subunit B type 1) regulates the synaptic vesicle cycle in the prefrontal cortex. The authors use a conditional knockout, with the PPP3R1 gene flanked by LoxP sites, and crossed this with a Camkii-Cre mousseline. The resulting mouse line is named CN in this study. Using extracellular records with multi-electrode arrays, they show that CN-KO mice have enhanced synaptic depression during 40 Hz stimulation (figure 3B and C). Basal synaptic transmission appears to be reduced as well since the fEPSP amplitude after a single stimulus is reduced, in particular at higher stimulation intensities. To demonstrate that this is a presynaptic effect, the authors performed additional recordings in the mossy fibre synapse in the hippocampus. In the mouse line used, PPP3R1 is removed from the presynaptic cells of this synapse (dentate gyrus granule cells), but not the postsynaptic CA3 pyramidal cells (Zeng 2001). At this synapse, they find a similar phenotype, with enhanced depression during a 40Hz train, demonstrating that the observed effect is presynaptic. The role of calcineurin as a regulator is justified in PMID:11672811 & 12691665 where it dephosphorylates essential proteins involved in synaptic vesicle cycle. |
| 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: | Zeng et. al. describe in detail how the CN-mouseline was created, and in which brain area PPP3R1 expression was removed. @ PMID:11733061 Fig2: Immunocytochemical studies demonstrate that high-frequency stimulation (20 Hz) leads to dephosphorylation of synapsin I at serine 551. Fig4: Perturbation of synapsin I dephosphorylation leads to impaired vesicle pool turnover at 20Hz. @ PMID:12691665 The paper reviews the dephosphorylation activity of calcineurin towards the different phosphoproteins involved in synaptic vesicle endocytosis. This enhances the evidence for the regulatory role of calcineurin in the synaptic vesicle cycle. @ PMID:11672811 |
| SynGO annotation ID: | 3953 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |