Cell-type dependent selectivity of CCK2R signaling (WP3679)

This pathway is based on Figure 7 of "Cell-Type Specific CCK2 Receptor Signaling Underlies the Cholecystokinin-Mediated Selective Excitation of Hippocampal Parvalbumin-Positive Fast-Spiking Basket Cells."(See Bibliography).The neuropeptide cholecystokinin (CCK) acts through its receptor CCK2R to achieve largely different functions in different types of cells. CCK, CCK2R, and CB1R have all been known to have substantial effects on anxiety and other mood disorders, and the PV+ interneurons have also been shown to be involved i na variety of cognitive functions. However, In PV+ basket cells and CCK+ basket cells, the CCK2 receptor uses different pathways to exert different effects on the two types of basket cells. For CCK+ basket cells, CCK2 receptors in neighboring pyramidal cells act through the Gq pathway to form endocannabinoids, which, through the cannabinoid receptor type 1 on the CCK+ basket cell, inhibit the release of the neurotransmitter GABA. In contrast, for PV+ basket cells, CCK2 receptors act through the pertussin-toxin sensitive Gi pathway to regulate the intracellular Ca2+ through ryanodine receptors. This pathway ultimately leads to activation of a non-selective cationic conductance to depolarize the PV+ basket cells.
last edited

Authors

AAR&Co, Mkutmon, Ariutta, Khanspers, DeSl, Egonw, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Annotations

Disease Ontology: pertussis

Cell Type Ontology: basket cell pyramidal neuron

Pathway Ontology: signaling pathway

Participants

Label Type Compact Identifier
IP3 receptor GeneProduct ensembl:ENSG00000150995
2-APB Metabolite wikidata:Q4596857
DAG Metabolite chebi:18035
YM022 Metabolite pubchem.compound:122130
cyclic ADPR Metabolite pubchem.compound:123847
Gi/0 GeneProduct ensembl:ENSG00000127955
Gq GeneProduct ensembl:ENSG00000156052
CCK2R GeneProduct ensembl:ENSG00000110148
8-NH2-cADPR Metabolite pubchem.compound:3081323
Flufenamic acid Metabolite chebi:42638
GABA Metabolite chemspider:116
RYR1 GeneProduct ensembl:ENSG00000196218
NEM Metabolite chemspider:4209
TRPC1 GeneProduct ensembl:ENSG00000144935
DAG lipase GeneProduct ensembl:ENSG00000134780
Ca 2+ Metabolite chebi:29108
Ryanodine Metabolite chemspider:16736002
CCK GeneProduct ensembl:ENSG00000187094
U-73122 Metabolite wikidata:Q27089044
PLCB1 GeneProduct ensembl:ENSG00000182621
CB1 GeneProduct ensembl:ENSG00000118432
YM022 Metabolite pubchem.compound:122130
ADP-Ribose cyclase GeneProduct ensembl:ENSG00000004468
CCK GeneProduct ensembl:ENSG00000187094
CCK2R GeneProduct ensembl:ENSG00000110148
Ca 2+ Metabolite chebi:29108
Ca 2+ Metabolite chebi:29108
Ca 2+ Metabolite chebi:29108
RYR2 GeneProduct ensembl:ENSG00000198626
RYR3 GeneProduct ensembl:ENSG00000198838
GABA Metabolite chemspider:116
GABA Metabolite chemspider:116
GABA Metabolite chemspider:116
Ca 2+ Metabolite chebi:29108
Ca 2+ Metabolite chebi:29108
Na + Metabolite chebi:29101
Na + Metabolite chebi:29101
Ca 2+ Metabolite chebi:29108
Ca 2+ Metabolite chebi:29108
RYR1 GeneProduct ensembl:ENSG00000196218
RYR2 GeneProduct ensembl:ENSG00000198626
RYR3 GeneProduct ensembl:ENSG00000198838

References

  1. Lee S-H, Soltesz I. Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells. J Physiol. 2011 Feb 15;589(Pt 4):891–902. PubMed Europe PMC Scholia
  2. Lee SY, Földy C, Szabadics J, Soltesz I. Cell-type-specific CCK2 receptor signaling underlies the cholecystokinin-mediated selective excitation of hippocampal parvalbumin-positive fast-spiking basket cells. J Neurosci. 2011 Jul 27;31(30):10993–1002. PubMed Europe PMC Scholia