| First Author | Tsumagari R | Year | 2020 |
| Journal | eNeuro | Volume | 7 |
| Issue | 2 | PubMed ID | 32033984 |
| Mgi Jnum | J:288365 | Mgi Id | MGI:6431961 |
| Doi | 10.1523/ENEURO.0319-19.2020 | Citation | Tsumagari R, et al. (2020) DGKgamma Knock-Out Mice Show Impairments in Cerebellar Motor Coordination, LTD, and the Dendritic Development of Purkinje Cells through the Activation of PKCgamma. eNeuro 7(2):ENEURO.0319-19.2020 |
| abstractText | Diacylglycerol kinase gamma (DGKgamma) regulates protein kinase C (PKC) activity by converting DG to phosphatidic acid (PA). DGKgamma directly interacts with PKCgamma and is phosphorylated by PKCgamma, resulting in the upregulation of lipid kinase activity. PKC dysfunction impairs motor coordination, indicating that the regulation of PKC activity is important for motor coordination. DGKgamma and PKC are abundantly expressed in cerebellar Purkinje cells. However, the physiological role of DGKgamma has not been elucidated. Therefore, we developed DGKgamma knock-out (KO) mice and tested their cerebellar motor coordination. In DGKgamma KO mice, cerebellar motor coordination and long-term depression (LTD) were impaired, and the dendrites of Purkinje cells from DGKgamma KO mice were significantly retracted. Interestingly, treatment with the cPKC inhibitor Go6976 (Go) rescued the dendritic retraction of primary cultured Purkinje cells from DGKgamma KO mice. In contrast, treatment with the PKC activator 12-o-tetradecanoylphorbol 13-acetate (TPA) reduced morphologic alterations in the dendrites of Purkinje cells from wild-type (WT) mice. In addition, we confirmed the upregulation of PKCgamma activity in the cerebellum of DGKgamma KO mice and rescued impaired LTD in DGKgamma KO mice with a PKCgamma-specific inhibitor. Furthermore, impairment of motor coordination observed in DGKgamma KO mice was rescued in tm1c mice with DGKgamma reexpression induced by the FLP-flippase recognition target (FRT) recombination system. These results indicate that DGKgamma is involved in cerebellar LTD and the dendritic development of Purkinje cells through the regulation of PKCgamma activity, and thus contributes to cerebellar motor coordination. |
