| First Author | Tsumagari R | Year | 2020 |
| Journal | Int J Mol Sci | Volume | 21 |
| Issue | 21 | PubMed ID | 33114041 |
| Mgi Jnum | J:305091 | Mgi Id | MGI:6681937 |
| Doi | 10.3390/ijms21217866 | Citation | Tsumagari R, et al. (2020) Precise Regulation of the Basal PKCgamma Activity by DGKgamma Is Crucial for Motor Coordination. Int J Mol Sci 21(21):7866 |
| abstractText | Diacylglycerol kinase gamma (DGKgamma) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C gamma (PKCgamma) activity. We previously reported that the basal PKCgamma upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKgamma knockout (KO) mice. However, the precise mechanism in impaired cerebellar LTD by upregulated PKCgamma has not been clearly understood. Therefore, we first produced Purkinje cell-specific DGKgamma KO (tm1d) mice to investigate the specific function of DGKgamma in Purkinje cells and confirmed that tm1d mice showed cerebellar motor dysfunction in the rotarod and beam tests, and the basal PKCgamma upregulation but not PKCalpha in the cerebellum of tm1d mice. Then, the LTD-induced chemical stimulation, K-glu (50 mM KCl + 100 microM, did not induce phosphorylation of PKCalpha and dissociation of GluR2 and glutamate receptor interacting protein (GRIP) in the acute cerebellar slices of tm1d mice. Furthermore, treatment with the PKCgamma inhibitor, scutellarin, rescued cerebellar LTD, with the phosphorylation of PKCalpha and the dissociation of GluR2 and GRIP. In addition, nonselective transient receptor potential cation channel type 3 (TRPC3) was negatively regulated by upregulated PKCgamma. These results demonstrated that DGKgamma contributes to cerebellar LTD by regulation of the basal PKCgamma activity. |
