Ethanol-induced changes in PKCe: From cell to behavior

The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCe is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCe expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCe expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCe to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCe, ethanol-induced changes in PKCe expression, the regulation of ethanol-induced PKCe activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCe-RACKe translocation in the presence of ethanol, and the existing literature on the role of PKCe in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.