BIS104 Note5

BIS104 Note5 - Lecture 5 Bio Sci 104 Protein and Lipid...

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Lecture 5 1 Bio Sci 104 Winter 2010 Protein and Lipid Trafficking-II What happens to lipids and proteins after they are made in the ER. How do the proteins destined to the Golgi, PM, secretion, and lysosomes get there? V. The default pathway- exocytosis from ER to Golgi to PM A. ER, Golgi, and PM are in constant intercommunication through a series of shuttling membrane vesicles. Golgi represents a “central hub” in this shuttling system. 1. Vesicles are constantly budding off each compartment taking lipid, membrane-associated proteins, and lumen contents with them. These transport vesicles are selective in terms of passengers . For example, vesicles transporting proteins from Golgi to PM exclude those proteins meant to stay in Golgi. 2. A highly organized process - with the biosynthetic-secretory pathway flowing from ER to Golgi to cell surface (with a branch to the lysosomes), whereas an endocytic pathway leads inward from the cell surface to the endosomes and lysosomes. B. The Golgi apparatus- 1. Major site of further glycosylation of proteins and lipids initially glycosylated in the ER 2. Golgi are also major site of synthesis of polysaccharides destined for extracellular deposition in plant cell walls and of the proteoglycans destined for the animal cell extracellular matrix. 3. Consists of a series of stacks of flattened membrane cisternae and many tiny vesicles. 4. Functionally and structurally divided into a cis -Golgi (initial location for entry of proteins and lipids passing through Golgi), a medial-Golgi, and a trans -Golgi (exit surface). 5. Golgi apparatus particularly large and prominent in cells specializing in secretion- e.g. pancreatic cells. C. Transport from ER to Golgi 1. Vesicles containing ER membrane, membrane proteins, and ER lumen contents constantly bud off a specialized region of the smooth ER (no ribosomes). This vesicle budding appears to have both selective and non-selective aspects. Some proteins have ER exit signals and are efficiently budded off ER and transported to Golgi. Others without specific signals can still be budded and transported to Golgi in a more general but less efficient "bulk-flow." ER exit signals not well understood. Incorrectly folded proteins remain in the ER until they fold properly, or they are degraded. 2. Vesicles budded from ER form a vesicular tubular cluster that is moved by motor proteins along microtubular tracks toward the -Golgi where they fuse.
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Lecture 5 2 3. The default pathway, therefore, is an exit from the ER and entry to the Golgi. How about the proteins that meant to stay in the ER (e.g. some chaperones, some glycosyl transferases, etc)? These have specialized sequences (e.g. many ER soluble proteins have KDEL (Lys, Asp, Glu, Leu) sequences, many ER membrane proteins have KKXX sequences) that form an ER retention signal . These proteins actually exit the ER and enter the Golgi, but are then retrieved back from the cis -Golgi into the ER by specialized recovery vesicles. Thus the KDEL and KKXX sequences are really a
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BIS104 Note5 - Lecture 5 Bio Sci 104 Protein and Lipid...

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