lecture 24&25 - LECTURES 24 & 25 23 & 26...

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BIOL 231 Reading: pp. 510-528; Probs: 70; exam III‘04,#3, 4; Exam III’05, #3; DVD 15.5, 15.8, 15.9, 15.10 I. The “Outbound” Pathway - from sites of synthesis to sites of residence/function (A) Protein & lipid asymmetry - different origins (1) Major phospholipids. have different phospholipid compositions. Most of the phosphatidylcholine (PC) is in the outer leaflet, while most of the phosphatidylethanolamine (PE) and phosphatidyl- serine (PS) are in the inner leaflet. All phospholipids are synthesized by enzymes on the cytoplasmic leaflet of the smooth ER, and 50% of them get translocated between leaflets non-specifically by a class of flippases called “scramblases;” this generates a mass and area balance between leaflets. In the plasma membrane, a different class of flippases with phospholipid specificity generate and maintain the characteristic asymmetry between leaflets. (2) Glycoproteins. Most membrane proteins are glycosylated (have branched chains of sugars added to specific amino acid residues) as they pass through the ER and Golgi apparatus. Because the enzymes that glycosylate the proteins are in the lumen of these organelles, the sugars are added only from that side . Since membrane proteins do not “flip” in the lipid bilayer, the glycosylated side of the proteins ends up on the extracellular surface once they have undergone traffic to the plasma membrane. (B) Destinations: secretion, cell surface, organelles (1) Secretion: proteins in the lumen can leave the cell; proteins inserted into the ER membrane can go to the plasma membrane (see fig 15-27 in ECB ). Critical info for localization = the HYDROPHOBIC SIGNAL SEQUENCE, which you know all about! But all organelles have specific proteins residing in their lumens and in their membranes, so some proteins must be halted along the secretory pathway, or diverted out of the pathway. (2) “HALT” – Proteins of the ER lumen: the 4 aa sequence KDEL at their C-terminus causes them to be retrieved from the Golgi back to the ER. They are not actually “halted” in the ER, but since there is constant 2 way traffic between the ER and the Golgi, on balance they spend most of their time in the ER. Perhaps we should think of it as a RETRIEVE signal. The critical targeting info = a short C- terminal aa sequence, KDEL. (See fig at left here).
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Targeting lysosomal enzymes to lysosomes Formation of clathrin-coated vesicles at surface of trans-Golgi (3) “DIVERGE” - Lysosomal enzymes. As they pass through the Golgi apparatus, Golgi enzymes recognize the degradative enzymes bound for the lysosome and modify their branched sugar chain to expose at the end the sugar mannose with a phosphate group attached to C-6:
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This note was uploaded on 12/18/2009 for the course BIOL 101 taught by Professor Wormer during the Fall '08 term at Purdue University-West Lafayette.

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lecture 24&25 - LECTURES 24 & 25 23 & 26...

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