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Wisniewska, J.

Publications and source records attributed to Wisniewska, J..

2 recordsLinked to original sources

Opposing effects of rewarding and aversive stimuli on D1 and D2 types of dopamine-sensitive neurons in the central amygdala

Dopamine-sensitive neurons are organized in two classes of cells, expressing D1- or D2- types of dopamine receptors, and are often mediating opposing aspects of reward-oriented behaviors. Here, we focused on dopamine-sensitive neurons in the central amygdala - a brain structure critically involved in processing emotion-related stimuli. We discovered that both dopamine receptor types are present in the central medial nucleus, while the lateral part is populated predominantly with DRD2 cells. Exposing mice to rewarding and aversive stimuli we studied DRD1 and DRD2 cells activity using in vivo two-photon calcium imaging in the CeM. We showed that cocaine and sugar predominantly increase the activity of DRD1(+) neurons and decrease DRD2(+) cells. Repeated exposure to cocaine, however, had the opposite effect on spontaneous excitatory synaptic transmission in the CeM than exposure to sugar. Quinine, an aversive stimulus, primarily engaged DRD2(+) neurons, activating predominantly those cells that were previously inhibited by sugar exposure. Our results show that though DRD1 and DRD2 populations are differentially engaged and regulated by appetitive/aversive stimuli, both participate in sugar, cocaine, and quinine processing.

neuroscience↗

DGKepsilon is S-palmitoylated at the cysteine located at the cytoplasmic end of its N-terminal transmembrane fragment

Diacylglycerol kinase-{varepsilon} (DGK{varepsilon}) catalyzes phosphorylation of diacylglycerol to phosphatidic acid with a unique specificity toward 1-stearoyl-2-arachidonoyl-sn-glycerol which is a backbone of phosphatidylinositol (PI). Owing to this specificity, DGK{varepsilon} is involved in the PI cycle maintaining the cellular level of phosphorylated PI derivatives of signaling activity, and was also found crucial for lipid metabolism. DGK{varepsilon} dysfunction is linked with the development of atypical hemolytic uremic syndrome and possibly other human diseases. Despite the DGK{varepsilon} significance, data on its regulation by co/posttranslational modifications are scarce. Here we report that DGK{varepsilon} is S-palmitoylated at Cys38/40 (mouse/human DGK{varepsilon}) located in the cytoplasmic end of its N-terminal putative transmembrane fragment. The S-palmitoylation of DGK{varepsilon} was revealed by metabolic labeling of cells with a palmitic acid analogue followed by click chemistry, and with acyl-biotin and acyl-PEG exchange assays. The S-acyltransferases zDHHC7 and zDHHC17, and the zDHHC6/16 tandem were found to catalyze DGK{varepsilon} S-palmitoylation which also increased the DGK{varepsilon} abundance. Mouse DGK{varepsilon}-Myc ectopically expressed in HEK293 cells localized to the endoplasmic reticulum where zDHHC6/16 reside and in small amounts also to the Golgi apparatus where zDHHC7 and zDHHC17 are present. The Cys38Ala substitution upregulated while hyperpalmitoylation of wild type DGK{varepsilon} reduced the kinase activity, indicating an inhibitory effect of the Cys38 S-palmitoylation. Additionally, the substitution of neighboring Pro31 with Ala also diminished the activity of DGK{varepsilon}. Taken together, our data indicate that S-palmitoylation can fine-tune DGK{varepsilon} activity in distinct cellular compartments, possibly by affecting the distance between the kinase and its substrate in a membrane.

cell biology↗