Protein Kinase Cγ (PKCγ): Function of Neuron Specific Isotype

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The gamma isotype of protein kinase C (PKCγ) is a member of the classical PKC (cPKC) subfamily which is activated by Ca²⁺ and diacyiglycerol in the presence of phosphatidylserine. Physiologically, PKCγ is activated by a mechanism coupled with receptor-mediated breakdown of inositol phospholipid as other cPKC isotypes such as PKCα and PKCβ. PKCγ is expressed solely in the brain and spinal cord and its localization is restricted to neurons, while PKCα and PKCβ are expressed in many tissues in addition to the brain. Within the brain, PKCγ 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 neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require PKCγ. Generation of mice deficient in PKCγ provided more information regarding the physiological functions of this isotype. PKCγ 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 γ-aminobutyric acid (GABA) receptor. Furthermore, a point mutation in the PKCγ 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.