Protein kinase Cγ (PKCγ):: Function of neuron specific isotype

The gamma isotype of protein kinase C (PKCgamma) is a member of the classical PKC (cPKC) subfamily which is activated by Ca2+ and diacylglycerol in the presence of phosphatidylserine. Physiologically, PKCgamma is activated by a mechanism coupled with receptor-mediated breakdown of inositol phospholipid as other cPKC isotypes such as PKCalpha and PKCbeta. PKCgamma is expressed solely in the brain and spinal cord and its localization is restricted to neurons, while PKCalpha and PKCbeta are expressed in many tissues in addition to the brain. Within the brain, PKCgamma is the most abundant in the cerebellum, hippocampus and cerebral cortex, where the existence of neuronal plasticity has been demonstrated. Pharmacological and electrophysiological studies have shown that several neu-ronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require PKCgamma. Generation of mice deficient in PKCgamma provided more information regarding the physiological functions of this isotype. PKCgamma deficient mice (i) have modified long term potentiation (LTP) in hippocampus, (ii) exhibit mild deficits in spatial and contextual learning (iii) exhibit impaired motor coordination due to persistent multiple innervations of climbing fibers on Purkinje cells, (iv) show attenuation of opioid receptor activation, and (v) show decreased effects of ethanol on type A of gamma-aminobutyric acid (GABA) receptor. Furthermore, a point mutation in the PKCgamma gene may contribute to retinitis pigmentosa and Parkinsonian syndrome. This article reviews the specific functions of this neuron-specific isotype of PKC in neuronal signal transduction.