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lec7.2011 - Lecture 7 Structure and Function of the ER and...

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Lecture 7: Structure and Function of the ER and Golgi; Transport between the ER and the Golgi 2/08/11 Reading: Alberts 766-799, 5 th edition Objectives • Outline the events in the synthesis and transport of membranes through the cell to the membrane. Describe how proteins are folded and modified in the ER • Understand the role of glycosylation in the processing of secretory/integral membrane proteins. Understand how carbohydrates are added to proteins in the Golgi and the ER • Elucidate the structure, function and polarization of the Golgi complex. Describe how proteins are transported between the ER and the Golgi Understand how vesicles fusing and budding move proteins through compartments in membrane traffic . Several distinct pathways through cytoplasm A. Biosynthetic-secretory pathway - synthesis in ER or Golgi (lipid, carbohydrate, protein); altered as pass through Golgi, moved to various locations (membrane, lysosome, plant cell vacuole, etc) 1. All proteins secreted from cell are initially made in ER & Golgi. I. Protein entry into RER followed by series of events; acted on by membrane or luminal enzymes A. Signal peptide on N-terminus of nascent polypeptide removed by proteolytic signal peptidase B. Carbohydrates added to protein by oligosaccharyltransferase (integral membrane protein) C. Reactions that assure proper folding driven by protein disulfide isomerase (forms & reshuffles disulfide bonds) & molecular chaperones (bind new proteins, promote folding); both occur in ER lumen D. Improperly folded proteins are destroyed 1. Transported out of ER into cytosol by reverse translocation (!), back through channels similar to those through which they entered; destroyed in cytosol by proteasome 2. This quality control ensures that aberrant proteins are not transported to other parts of cell 3. In severe cystic fibrosis, mutant CFTR does not reach cell surface; it is destroyed II. Why is ER so well-suited & ideally constructed for its role as port of entry for secretory proteins? A. Large surface area to which many ribosomes can attach (~13 million/liver cell) B. Lumen environment favors correct folding & assembly; place to sequester these proteins from other new ones & allows them to be dispatched toward ultimate destination The Endoplasmic Reticulum (ER): Membrane Biosynthesis in the ER I . Membranes thought to arise from preexisting ones - newly made proteins, lipids inserted into existing membranes in ER; altered as move through cell; each compartment has unique membranes A. Membrane moves from ER to everywhere else; modified by enzymes in various
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compartments B. Cell membranes are asymmetric (established in ER & preserved); components at ER cisternal
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