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, PKC alpha, PKC beta I/beta II, and PKC gamma. PKC alpha and PKC beta I/beta II are expressed in the cells of various tissues including the brain, while PKC gamma 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 PKC alpha and PKC gamma. Previous studies have shown that PKC alpha is involved in the induction of long-term depression (LTD) at parallel fiber-Purkinje cell synapses. On the other hand, analysis of PKC gamma-deficient mice has revealed that PKC gamma plays a critical role in eliminating supernumerary climbing fiber synapses from developing Purkinje cells. Although why PKC alpha has no compensatory action in climbing fiber pruning in PKC gamma-deficient Purkinje cells had so far remained unclear, we have recently demonstrated that PKC alpha is also capable of pruning supernumerary climbing fiber synapses, but the expression levels of PKC alpha are too low to achieve pruning in PKC gamma-null Purkinje cells. Notably, although PKC gamma 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 PKC alpha in developing Purkinje cells and a possible involvement of PKC gamma in motor coordination in the mature cerebellum.