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Dopamine and the phosphorylated dopamine transporter are increased in the diacylglycerol kinase η‐knockout mouse brain
Author(s) -
Asami Maho,
Suzuki Yuji,
Sakane Fumio
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14059
Subject(s) - dopamine transporter , diacylglycerol kinase , dopamine , dopaminergic , phosphorylation , endocrinology , dopamine plasma membrane transport proteins , medicine , kinase , knockout mouse , chemistry , biology , microbiology and biotechnology , neuroscience , protein kinase c , biochemistry , receptor
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.