| Annotated protein: | Cannabinoid receptor 1 (CB-R) (CB1) (Brain-type cannabinoid receptor). Gene symbol: CNR1. Taxonomy: Mus musculus (Mouse). Uniprot ID: P47746 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CNR1 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of ATP metabolic process in the presynapse |
| Synapse type(s): | hippocampus, GABAergic |
| Annotated paper: | Benard G, et al. "Mitochondrial CB(1) receptors regulate neuronal energy metabolism" Nat Neurosci. 2012 Mar 4;15(4):558-64 PMID:22388959 |
| Figure(s): | Figure 3, 4 |
| Annotation description: | CB1 localized in mitochondria (mtCB1) regulates mitochondrial respiration: using purified mitochondria from wild-type (WT) or CB1-/- brains it is shown that treatment with CB1 receptor agonists WIN (Figure 3) or THC (Figure 4a-c) reduces respiration, cAMP levels and PKA activity in neuronal mitochondria. Depolarization of CA1 postsynaptic pyramidal neurons mobilizes endocannabinoids, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission in a process known as depolarization-induced suppression of inhibition (DSI), an endocannabinoid-dependent form of short-term plasticity of inhibitory neurotransmission in the hippocampus. DSI is fully blocked by cell-permeant CB1 antagonists (AM251) but only partially blocked by cell-impermeant CB1 antagonists (hemopressin) (Figure 6A), indicating a contribution of mtCB1 activation in DSI. In addition, suppression similar to the one obtained by DSI is found only with cell-permeant agonists of CB1 (HU210) but not with cell-impermeant versions (biotinylated-HU210). Also, HU210 occludes DSI completely, whereas biotinylated-HU210 only occludes it partially, suggesting again a contribution of mtCB1 activation for DSI (Figure 6C). mtCB1 activation also results in reduced mitochondrial respiration and, additionally, direct inhibition of complex I activity using rotenone also mimics DSI, suggesting that endocannabinoid-induced DSI depends on mitochondrial respiration, which would be controlled by mtCB1 (Figure 7). |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Biochemical fractionation (generic) |
| Annotator(s): | Ryan J. Farrell (ORCID:0000-0003-4022-8707) Ghazaleh Ashrafi (ORCID:0000-0001-7480-0826) Camila Pulido (ORCID:0000-0002-5648-066X) Jaime de Juan-Sanz (ORCID:0000-0002-1212-5623) Timothy Ryan (ORCID:0000-0003-2533-9548) |
| Lab: | Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA |
| Additional literature: | Figure 1: Requirement of mtCB1 receptors for cannabinoid effects on mitochondrial respiration. @ PMID:27828947 |
| SynGO annotation ID: | 795 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |