Protein Kinase C in the Cerebellum: Its Significance and Remaining Conundrums
Protein kinase C (PKC), a family of serine/threonine protein kinases, mediates a myriad of patho-physiological cellular events in various tissues. The originally discovered PKC (conventional) requires the binding of diacylglycerol and Ca2+ for full activation. The conventional PKC consists of four isoforms, PKCα, PKCβI/βII, and PKCγ. PKCα and PKCβI/βII are expressed in the cells of various tissues including the brain, while PKCγ is present specifically in neurons of the brain and spinal cord. The cerebellum expresses the largest amount of PKC with all its four isoforms. Purkinje cells express PKCα and PKCγ. Previous studies have shown that PKCα is involved in the induction of long-term depression (LTD) at parallel fiber–Purkinje cell synapses. On the other hand, analysis of PKCγ-deficient mice has revealed that PKCγ plays a critical role in eliminating supernumerary climbing fiber synapses from developing Purkinje cells. Although why PKCα has no compensatory action in climbing fiber pruning in PKCγ-deficient Purkinje cells had so far remained unclear, we have recently demonstrated that PKCα is also capable of pruning supernumerary climbing fiber synapses, but the expression levels of PKCα are too low to achieve pruning in PKCγ-null Purkinje cells. Notably, although PKCγ is most abundant in Purkinje cells, its physiological role in mature Purkinje cells remained totally unknown. In addition to a concise review of the physiological and pathological roles of conventional PKCs in Purkinje cells, this report postulates a contribution of PKCα in developing Purkinje cells and a possible involvement of PKCγ in motor coordination in the mature cerebellum.
KeywordsProtein kinase C PKCγ Cerebellum Purkinje cell LTD
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Conflict of Interest
The author declares that there are no conflicts of interest.
- 7.Ase K, Saito N, Shearman MS, Kikkawa U, Ono Y, Igarashi K, et al. Distinct cellular expression of beta I- and beta II-subspecies of protein kinase C in rat cerebellum. J Neurosci Off J Soc Neurosci. 1988;8:3850–6.Google Scholar
- 9.Takahashi N, Shuvaev AN, Konno A, Matsuzaki Y, Watanave M, Hirai H. Regulatory connection between the expression level of classical protein kinase C and pruning of climbing fibers from cerebellar Purkinje cells. J Neurochem. 2017; https://doi.org/10.1111/jnc.14239.
- 13.Kano M, Hashimoto K, Tabata T. Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination. Philos Trans R Soc Lond Ser B Biol Sci. 2008;363:2173–86. https://doi.org/10.1098/rstb.2008.2270.CrossRefGoogle Scholar
- 20.Chung HJ, Xia J, Scannevin RH, Zhang X, Huganir RL. Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J Neurosci Off J Soc Neurosci. 2000;20:7258–67.Google Scholar
- 22.Shuvaev AN, Horiuchi H, Seki T, Goenawan H, Irie T, Iizuka A, et al. Mutant PKCgamma in spinocerebellar ataxia type 14 disrupts synapse elimination and long-term depression in Purkinje cells in vivo. J Neurosci Off J Soc Neurosci. 2011;31:14324–34. https://doi.org/10.1523/jneurosci.5530-10.2011.CrossRefGoogle Scholar