BIOMG 1350 1st Edition Lecture 11Outline of Last Lecture I. Sorting ProteinsOutline of Current Lecture II. Secretion PathwaysIII.Events in the ERIV. Transport by GolgiV. Protein modification by GolgiCurrent Lecture- The ER is a network of membranes spread throughout the cell- ER is the entry point for membrane and luminal proteins of the ER, Golgi, endosomes, lysosomes, and of secreted and plasma membrane proteins (all part of the secretory protein)- Endocytic Pathway- ER:o Many proteins are glycosylated on asparagine in the ER: N-linked glycosylation (occurs in lumen NOT cytosol) it will not get glycosylated if it a cytosolic protein. The glycosylated protein is topologically on the outside of the cello Called N-linked because N is the single letter code for asparagineo Chaperones assist protein folding and prevent misfolded proteins form leaving the ER Correct protein folding often involves disulfide bond formation between appropriate cysteine residues If the chaperone cant fold a protein properly, the protein is degraded Chaperone machinery must be appropriate for the cell if there are too many unfolded proteins, it is controlled by ER quality control system Not enough chaperones?  Unfolded protein response pathway- There are receptors in ER that can identify misfolded proteins they can identify these proteins through hydrophobic bonds- Ex. CFTR: chloride channel normally found in plasma membrane inunaffected membrane. In cystic fibrosis it is defective  causes retention and degradation of the CFTR protein in the ER by the These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Quality Control System. Mutant CFTR does not leave the ER and isdegraded  they lack a chlorine channel that most cells have- ER Golgi:o Same orientation of lipid bilayer in ER and Golgi, topology (orientation) is preservedo Mediated by COPII: Highly selective another protein will identify it in the ER, incorporated in ton transport molecules Adaptors capture cargo by binding to the cytoplasmic tails Coat protein ( in cytosol) bind adaptors to form a vesicle Vesicle pinches it is uncoated and ready to fuse with target membrane Has determinants to help it find where to go:- RAB GTP Cycle and SNARES direct transport vesicles to their targetmembrane. RAB GTP is on the vesicle Rab GAP is found on target membrane, there it hydolizes Rab GTP Rab to Rab GDP tobe reused. Rab GTP must hydorlize before T and V SNARE can drive combining process- In active state, it will bind to specific tethering protein on target membrane- Has a GTPase cycle!- VSNARE (identity tags):o Transmembrane proteinso Specific for each transport stepo On target membrane there is a specific TSNARE they bind to each other forces fusion between two membranes and carbon is releasedo SNARES play a central role in membrane fusiono T AND VSNARE twist together but machinery works them apart and T SNARE is left in the membrane- Golgi Membrane:o Topology of lipid membranes and membrane proteins is preservedo Membrane enclosed sacs called cisternao Process:Proteins enter on cis cisterna side of Golgi Sequential modification of oligosaccharide chains Protein sorting in trans Golgi network This is true for water soluble luminal secretory proteins and proteins embedded in the membrane Constitutive Pathway:- Always a protein that goes to plasma membrane Regulated Secretion:- Will not occur until it is told to do so Pathways organized by microtubules by “molecular