Dopamine and the phosphorylated dopamine transporter are increased in the diacylglycerol kinase η-knockout mouse brain.
Parkinson's disease
bipolar disorder
diacylglycerol kinase
dopamine
protein kinase C
schizophrenia
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
26
01
2021
received:
26
11
2020
accepted:
09
02
2021
pubmed:
19
2
2021
medline:
24
7
2021
entrez:
18
2
2021
Statut:
ppublish
Résumé
The molecular mechanisms generating the mania-like abnormal behaviors caused by diacylglycerol (DG) kinase (DGK) η deficiency remain unclear. Here, we found that DGKη knockout markedly increased dopamine (DA) levels in the midbrain (DA-producing region, 2.8-fold) and cerebral cortex (DA projection region, 1.2-fold). Moreover, DGKη deficiency significantly augmented phosphorylated DA transporter (DAT) levels (1.4-fold increase), which induce DA efflux to the synaptic cleft, in the cerebral cortex. Moreover, phosphorylation levels of protein kinase C-β, which is activated by DG and involved in DAT phosphorylation, were also increased. DAT expressed in Neuro-2a cells recruited DGKη to the plasma membrane and colocalized with it. These results strongly suggest that dopaminergic hyperfunction caused by DGKη deficiency in the brain leads to mania-like behaviors.
Identifiants
pubmed: 33599293
doi: 10.1002/1873-3468.14059
doi:
Substances chimiques
Dopamine Plasma Membrane Transport Proteins
0
Dgkh protein, mouse
EC 2.7.1.107
Diacylglycerol Kinase
EC 2.7.1.107
Protein Kinase C beta
EC 2.7.11.13
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1313-1321Informations de copyright
© 2021 Federation of European Biochemical Societies.
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