PKC-gamma calcium signaling in ataxia (Homo sapiens)

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1cerebellar Purkinje cellsERLegendActivating mutationLigandsCA8TRPC3PI(3,4,5)P3IP3CACNA1AGNAQGRIA1Na+RYR3Ca2+PRKCGDAGIP3R1PIP2PLCB1HOMER3GRM1PPPDK1PPPLCB2PLCB3PLCB4GNA11GNA14GNA15GRIA2GRIA3GRIA4ATP2B2Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Ca2+Na+Inactivating mutation


Description

PKC-gamma calcium-signaling pathway in Ataxia.

Upon ligand binding, the mGluR1 receptor is followed by activation of Gq causing PLC-mediated hydrolysis of PIP2 into IP3 and DAG. Binding of IP3 to the IP3R1 induces Ca2+ release from the endoplasmic reticulum to the cytoplasm. This step is controlled by CAR8, which can inhibit binding of IP3 to the IP3R1. Simultaneous binding of Ca2+ to PKC-gamma C2 domain and of DAG to the C1 domain of PKC-gamma induce translocation of PKC-gamma to the plasma membrane. There, the pseudosubstrate is released from the kinase domain, allowing phosphorylation of downstream target proteins, including GRIA1. PKC exerts an inhibitory effect on TRPC3 channel either directly through phosphorylation or indirectly. A rise of the intracellular calcium concentration can also be mediated by the voltage-gated Ca2+ channel Cav2.1 or TRPC3. Conversely, PMCA2 can efficiently remove Ca2+ from the cytoplasm.

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Bibliography

  1. Shimobayashi E, Kapfhammer JP; ''Calcium Signaling, PKC Gamma, IP3R1 and CAR8 Link Spinocerebellar Ataxias and Purkinje Cell Dendritic Development.''; Curr Neuropharmacol, 2018 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
129748view01:55, 22 May 2024EweitzModified title
128777view23:29, 21 February 2024EweitzOntology Term : 'Purkinje cell' added !
128776view23:28, 21 February 2024EweitzFix layering issue seen only in site rendering
128775view23:26, 21 February 2024EweitzOntology Term : 'CL:0000118' removed !
128774view23:25, 21 February 2024EweitzOntology Term : 'basket cell' added !
128773view23:25, 21 February 2024EweitzOntology Term : 'pyramidal neuron' added !
108400view00:13, 17 December 2019Khanspersupdate phosphosite
108397view00:04, 17 December 2019Khanspersupdated phosphosite
108395view19:35, 16 December 2019Khanspersminor layout change
108386view04:05, 16 December 2019KhanspersModified description
108385view04:02, 16 December 2019KhanspersModified description
108374view19:20, 13 December 2019EgonwConverted an old HMDB id to the new style.
108373view19:12, 13 December 2019EgonwReplaced secondary ChEBI identifiers with a primary identifiers.
108372view18:42, 13 December 2019KhanspersModified description
108369view01:32, 13 December 2019KhanspersOntology Term : 'altered calcium homeostasis pathway' added !
108368view01:31, 13 December 2019KhanspersOntology Term : 'neurodegenerative disease' added !
108367view01:31, 13 December 2019KhanspersOntology Term : 'hereditary ataxia' added !
108366view01:28, 13 December 2019KhanspersModified title
108365view01:27, 13 December 2019KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ATP2B2GeneProductENSG00000157087 (Ensembl)
CA8GeneProductENSG00000178538 (Ensembl)
CACNA1AGeneProductENSG00000141837 (Ensembl)
Ca2+MetaboliteCHEBI:3308 (ChEBI)
DAGMetaboliteCHEBI:4481 (ChEBI)
GNA11GeneProductENSG00000088256 (Ensembl)
GNA14GeneProductENSG00000156049 (Ensembl)
GNA15GeneProductENSG00000060558 (Ensembl)
GNAQGeneProductENSG00000156052 (Ensembl)
GRIA1GeneProductENSG00000155511 (Ensembl)
GRIA2GeneProductENSG00000120251 (Ensembl)
GRIA3GeneProductENSG00000125675 (Ensembl)
GRIA4GeneProductENSG00000152578 (Ensembl)
GRM1GeneProductENSG00000152822 (Ensembl)
HOMER3GeneProductENSG00000051128 (Ensembl)
IP3MetaboliteHMDB01498 (HMDB)
IP3R1GeneProductENSG00000150995 (Ensembl)
Na+MetaboliteCHEBI:29101 (ChEBI)
PDK1GeneProductENSG00000152256 (Ensembl)
PI(3,4,5)P3MetaboliteQ3078767 (Wikidata)
PIP2MetaboliteQ3083814 (Wikidata)
PLCB1GeneProductENSG00000182621 (Ensembl)
PLCB2GeneProductENSG00000137841 (Ensembl)
PLCB3GeneProductENSG00000149782 (Ensembl)
PLCB4GeneProductENSG00000101333 (Ensembl)
PRKCGGeneProductENSG00000126583 (Ensembl)
RYR3GeneProductENSG00000198838 (Ensembl)
TRPC3GeneProductENSG00000138741 (Ensembl)

Annotated Interactions

No annotated interactions

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