A MOLECULAR-BASIS FOR RETINOL STIMULATION OF VESICLE BUDDING IN-VIVO AND IN-VITRO

Retinol stimulates the formation of transition vesicles in situ and in all free systems based on rat liver. The stimulation is on vesicle fo rmation from transitional endoplasmic reticulum and not on vesicle fus ion with donor membranes. Vesicle budding in the cell free system requ ires a nucleoside triphosphate and is sensitive to inhibition by thiol reagents. In this report we develop and test a model whereby a retino l-modulated NADH:protein disulfide reductase (NADH oxidase) with prote in disulfide-thiol interchange activity is implicated in the vesicle b udding mechanism. The protein has the ability to restore activity to s crambled, inactive RNase A and is stimulated or inhibited by retinol d epending on the redox environment. Under reducing conditions and in th e presence of a chemical reductant such as GSH, the partial reaction s timulated by retinol appears to be the oxidation of membrane thiols. T his is the first report of an enzymatic mechanism to explain specific retinol effects both in vivo and in vitro on membrane trafficking not given by retinoic acid.