This research proposal describes a plan to characterize the intracellular biosynthetic pathway of a rat liver membrane glycoprotein implicated in taurocholate bile acid transport and present in the polarized hepatocyte at the apical or bile canalicular membrane. The biogenesis of this molecule will be analyzed using metabolic labeling in combination with subcellular fractionation, immunoadsorption and immunoblotting. With such an approach, the taurocholate transporter will be followed from its glycosylatin in the Golgi to the sinusoidal membrane and then to the bile canalicular membrane where this glycoprotein carries out its unction. The question tap be answered is """"""""At what point does this glycoprotein, which functions at the bile canaliculus, sort itself from glycoproteins with other functions that are restricted to the sinusoidal membrane?"""""""" Answers to this question will clarify our understanding of intracellular glycoprotein biogenesis and establish a foundation for future investigation into the pathogenesis of hepatobiliary disease.
