Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination

Department of Animal Functional Genomics of Advanced Science Research Promotion Center, Mie University Organization for the Promotion of Regional Innovation, Tsu 514-8507, Japan

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(21), 7866; https://doi.org/10.3390/ijms21217866

Received: 18 September 2020 / Revised: 19 October 2020 / Accepted: 21 October 2020 / Published: 23 October 2020

(This article belongs to the Special Issue Diacylglycerol Kinases in Signal Transduction)

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Abstract

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. View Full-Text

Keywords: DGKγ; PKCγ; LTD; motor coordination; TRPC3

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MDPI and ACS Style

Tsumagari, R.; Maruo, K.; Kakizawa, S.; Ueda, S.; Yamanoue, M.; Saito, H.; Suzuki, N.; Shirai, Y. Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination. Int. J. Mol. Sci. 2020, 21, 7866. https://doi.org/10.3390/ijms21217866

AMA Style

Tsumagari R, Maruo K, Kakizawa S, Ueda S, Yamanoue M, Saito H, Suzuki N, Shirai Y. Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination. International Journal of Molecular Sciences. 2020; 21(21):7866. https://doi.org/10.3390/ijms21217866

Chicago/Turabian Style

Tsumagari, Ryosuke, Kenta Maruo, Sho Kakizawa, Shuji Ueda, Minoru Yamanoue, Hiromitsu Saito, Noboru Suzuki, and Yasuhito Shirai. 2020. "Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination" International Journal of Molecular Sciences 21, no. 21: 7866. https://doi.org/10.3390/ijms21217866

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Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination

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