Opioid peptides regulate neuronal shape and function. I will test the hypothesis that the role of the opioid receptor the cortical cytoskeleton, neuronal shape, and neuronal function, i.e., neuro- transmitter secretion. Neuronal shape and function are tightly interrelated events. An integral and important part of this molecular interaction circuit is the membrane receptor, which stimulates specific signaling pathways to mediate information from the microenvironment. This chain of molecular interactions leads to normal neuronal function.
The specific aims are to express and overexpress the mouse delta-opioid receptor in PC12 and NG108x15 cell lines and (a) establish the regulation of neuronal shape by showing that the delta-opioid receptor regulates neuritic process outgrowth; (b) determine the involvement of kinases Src, FAK in the signal transduction pathway of the delta-opioid receptor; (c) study the mechanism of regulation of the cortical cytoskeleton (posttranslational modifications of vinculin and cortactin). For the proposed studies I will use a combination of tissue culture, biochemical, immunocytochemical, and gene transfer techniques. My goal is to provide a better understanding of how the opioid receptors regulate neural function, and thus set the stage for better therapeutic interventions with opiates.
