MEMBRANE PROTEIN TRAFFIC IN NORMAL AND TRANSFORMED CELLS

本项目的总体目标是了解

The overall goal of this Program Project is to understand the molecular mechanisms involved in the control of protein and membrane traffic in normal and transformed cells. It consists of seven individual projects: Project 1: The goal of this project is to characterize Golgi subcompartments and to identify functionally important membrane proteins found in these subcompartments. The trafficking of the lysosomal Man-6-P receptor (46 Kd) through Golgi subcompartments will also be investigated in normal and transformed cells. Project 2: This project takes advantage of the genetic approach and the availability of mutants defective in specific steps along the secretory pathway to identify proteins or regions of proteins that are important in targeting along the exocytic pathway. One such mutant to be investigated has a defective gene that appears to be a member of the ras oncogene family. Project 3: The goal of this project is to investigate the role of protein conformation on signaling transport along the secretory pathway using viral membrane proteins as models. Project 4: This project will investigate the role of the binding protein BiP in post-translational processing and ER to Golgi transit of nascent secretory and membrane proteins in normal and transformed cells. Project 5: The purpose of this project is to determine the mechanisms of sorting and traffic control during endocytosis using closely related Fc receptors in normal and transformed cells expressing this receptor from clone cDNAs. Project 6: The goals of this project are to define the molecular basis for the transient failure of the membrane protein, glycophorin, to be segregated in the ER in transformed Friend Erytholeukemic cells, and to attempt to identify sorter proteins and carrier proteins involved in control of vesicular membrane traffic. Project 7: Hybrid proteins generated by gene fusion and expression technologies have been shown to be blocked at various steps along the biosynthetic pathway. In this project the precise site of the blockage and the molecular features responsible for the blockages will be investigated.