Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination
Diacylglycerol kinase γ (DGKγ) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C γ (PKCγ) activity. We previously reported that the basal PKCγ upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKγ knocko...
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2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/7866 |
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| author | Ryosuke Tsumagari Kenta Maruo Sho Kakizawa Shuji Ueda Minoru Yamanoue Hiromitsu Saito Noboru Suzuki Yasuhito Shirai |
| author_facet | Ryosuke Tsumagari Kenta Maruo Sho Kakizawa Shuji Ueda Minoru Yamanoue Hiromitsu Saito Noboru Suzuki Yasuhito Shirai |
| author_sort | Ryosuke Tsumagari |
| collection | DOAJ |
| description | Diacylglycerol kinase γ (DGKγ) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C γ (PKCγ) activity. We previously reported that the basal PKCγ upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKγ knockout (KO) mice. However, the precise mechanism in impaired cerebellar LTD by upregulated PKCγ has not been clearly understood. Therefore, we first produced Purkinje cell-specific DGKγ KO (tm1d) mice to investigate the specific function of DGKγ in Purkinje cells and confirmed that tm1d mice showed cerebellar motor dysfunction in the rotarod and beam tests, and the basal PKCγ upregulation but not PKCα in the cerebellum of tm1d mice. Then, the LTD-induced chemical stimulation, K-glu (50 mM KCl + 100 µM, did not induce phosphorylation of PKCα and dissociation of GluR2 and glutamate receptor interacting protein (GRIP) in the acute cerebellar slices of tm1d mice. Furthermore, treatment with the PKCγ inhibitor, scutellarin, rescued cerebellar LTD, with the phosphorylation of PKCα and the dissociation of GluR2 and GRIP. In addition, nonselective transient receptor potential cation channel type 3 (TRPC3) was negatively regulated by upregulated PKCγ. These results demonstrated that DGKγ contributes to cerebellar LTD by regulation of the basal PKCγ activity. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:24:09Z |
| publishDate | 2020-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f08ab2dc66994f489b5bcfaf474de8dc2023-11-20T18:16:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121786610.3390/ijms21217866Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor CoordinationRyosuke Tsumagari0Kenta Maruo1Sho Kakizawa2Shuji Ueda3Minoru Yamanoue4Hiromitsu Saito5Noboru Suzuki6Yasuhito Shirai7Department of Applied Chemistry in Bioscience, Graduate School of Agricultural Sciences, Kobe University, Kobe 657-8501, JapanDepartment of Applied Chemistry in Bioscience, Graduate School of Agricultural Sciences, Kobe University, Kobe 657-8501, JapanDepartment of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, JapanDepartment of Applied Chemistry in Bioscience, Graduate School of Agricultural Sciences, Kobe University, Kobe 657-8501, JapanDepartment of Applied Chemistry in Bioscience, Graduate School of Agricultural Sciences, Kobe University, Kobe 657-8501, JapanDepartment of Animal Functional Genomics of Advanced Science Research Promotion Center, Mie University Organization for the Promotion of Regional Innovation, Tsu 514-8507, JapanDepartment of Animal Functional Genomics of Advanced Science Research Promotion Center, Mie University Organization for the Promotion of Regional Innovation, Tsu 514-8507, JapanDepartment of Applied Chemistry in Bioscience, Graduate School of Agricultural Sciences, Kobe University, Kobe 657-8501, JapanDiacylglycerol kinase γ (DGKγ) is a lipid kinase to convert diacylglycerol (DG) to phosphatidic acid (PA) and indirectly regulates protein kinase C γ (PKCγ) activity. We previously reported that the basal PKCγ upregulation impairs cerebellar long-term depression (LTD) in the conventional DGKγ knockout (KO) mice. However, the precise mechanism in impaired cerebellar LTD by upregulated PKCγ has not been clearly understood. Therefore, we first produced Purkinje cell-specific DGKγ KO (tm1d) mice to investigate the specific function of DGKγ in Purkinje cells and confirmed that tm1d mice showed cerebellar motor dysfunction in the rotarod and beam tests, and the basal PKCγ upregulation but not PKCα in the cerebellum of tm1d mice. Then, the LTD-induced chemical stimulation, K-glu (50 mM KCl + 100 µM, did not induce phosphorylation of PKCα and dissociation of GluR2 and glutamate receptor interacting protein (GRIP) in the acute cerebellar slices of tm1d mice. Furthermore, treatment with the PKCγ inhibitor, scutellarin, rescued cerebellar LTD, with the phosphorylation of PKCα and the dissociation of GluR2 and GRIP. In addition, nonselective transient receptor potential cation channel type 3 (TRPC3) was negatively regulated by upregulated PKCγ. These results demonstrated that DGKγ contributes to cerebellar LTD by regulation of the basal PKCγ activity.https://www.mdpi.com/1422-0067/21/21/7866DGKγPKCγLTDmotor coordinationTRPC3 |
| spellingShingle | Ryosuke Tsumagari Kenta Maruo Sho Kakizawa Shuji Ueda Minoru Yamanoue Hiromitsu Saito Noboru Suzuki Yasuhito Shirai Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination International Journal of Molecular Sciences DGKγ PKCγ LTD motor coordination TRPC3 |
| title | Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination |
| title_full | Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination |
| title_fullStr | Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination |
| title_full_unstemmed | Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination |
| title_short | Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination |
| title_sort | precise regulation of the basal pkcγ activity by dgkγ is crucial for motor coordination |
| topic | DGKγ PKCγ LTD motor coordination TRPC3 |
| url | https://www.mdpi.com/1422-0067/21/21/7866 |
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