PI: Smith IBN-9723384 The first cellular step in vision is phototransduction, when light energy is captured by molecular mechanisms that finally lead to a nerve signal to the brain. A cascade of biochemical reactions occurs in the photoreceptor cell, and one of the key steps is the activation of a class of proteins called G-proteins. The activation occurs by phosphorylation, the addition of a phosphate group to protein; subsequent deactivation involves dephosphorylation. One of the proteins regulating the rate and amount of phosphorylation is called arrestin. While much research has studied the activation of the light signal, few have worked on the way the signal is turned off, and that is the focus here. This collaborative project combines approaches from molecular biology, biochemistry and cellular physiology to investigate the up- and down-regulation of G-protein linked membrane receptor molecules. The system used is the photoreceptor of the horseshoe crab, Limulus, which has been a model for invertebrate photoreception for decades and also provides excellent comparisons to our knowledge of vertebrate phototransduction. Results from this work will add critical understanding about regulation of visual processes, and have an impact extending beyond photoreception and vision to signal transduction in cell communication and to cellular biology in general.