DGKγ Knock-Out Mice Show Impairments in Cerebellar Motor Coordination, LTD, and the Dendritic Development of Purkinje Cells through the Activation of PKCγ.

Diacylglycerol kinase γ (DGKγ) regulates protein kinase C activity by converting DG to phosphatidic acid (PA). DGKγ directly interacts with and is phosphorylated by resulting in the upregulation of lipid kinase activity. dysfunction impairs motor coordination, indicating that the regulation of duanyu1531 activity is important for motor coordination. DGKγ and duanyu1531 are abundantly expressed in cerebellar Purkinje cells. However, the physiological role of DGKγ has not been elucidated. Therefore, we developed DGKγ knock-out (KO) mice and tested their cerebellar motor coordination. In DGKγ KO mice, cerebellar motor coordination and long-term depression (LTD) were impaired, and the dendrites of Purkinje cells from DGKγ KO mice were significantly retracted. Interestingly, treatment with the inhibitor Gö6976 (Gö) rescued the dendritic retraction of primary cultured Purkinje cells from DGKγ KO mice. In contrast, treatment with the duanyu1531 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 duanyu1531γ activity in the cerebellum of DGKγ KO mice and rescued impaired LTD in DGKγ KO mice with a inhibitor. Furthermore, impairment of motor coordination observed in DGKγ KO mice was rescued in tm1c mice with DGKγ reexpression induced by the FLP-flippase recognition target (FRT) recombination system. These results indicate that DGKγ is involved in cerebellar LTD and the dendritic development of Purkinje cells through the regulation of duanyu1531γ activity, and thus contributes to cerebellar motor coordination.

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