Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination
Open Access
- 23 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (21), 7866
- https://doi.org/10.3390/ijms21217866
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.This publication has 50 references indexed in Scilit:
- Functional and Physical Interaction of Diacylglycerol Kinase ζ with Protein Kinase Cα Is Required for Cerebellar Long-Term DepressionJournal of Neuroscience, 2015
- Mutant PKCγ in Spinocerebellar Ataxia Type 14 Disrupts Synapse Elimination and Long-Term Depression in Purkinje CellsIn VivoJournal of Neuroscience, 2011
- Group 1 mGluR-Dependent Synaptic Long-Term Depression: Mechanisms and Implications for Circuitry and DiseaseNeuron, 2010
- Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse eliminationPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2008
- A Unique PDZ Ligand in PKCα Confers Induction of Cerebellar Long-Term Synaptic DepressionNeuron, 2004
- Requirement of AMPA Receptor GluR2 Phosphorylation for Cerebellar Long-Term DepressionScience, 2003
- The molecular organization of cerebellar long-term depressionNature Reviews Neuroscience, 2002
- Protein Kinase C (PKC ): Function of Neuron Specific IsotypeThe Journal of Biochemistry, 2002
- Cerebellar Long-Term Depression Requires PKC-Regulated Interactions between GluR2/3 and PDZ Domain–Containing ProteinsNeuron, 2000
- Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKCγ mutant miceCell, 1995