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Chapter 4

Protein Sorting and
Vesicle Traffic

 
Cells contain numerous metabolic compartments and membranes that have unique sets of proteins. Nearly all of these proteins are synthesized in the cytosol. How do they reach their correct destinations? Proteins have sorting domains that act as address labels; there is a unique label for each destination. These sorting domains are usually short segments of polypeptide that may or may not be removed after the proteins reach their destination.
      Many sorting domains interact with proteinaceous pores in membranes. Such pores consist of numerous different polypeptides and are unique to each organelle. Passage of a polypeptide through a pore requires the participation of chaperones and energy in the form of ATP, GTP, or both. Chaperones help keep proteins unfolded in the cytosol before passage through the pore and are required to fold the protein correctly once it has crossed the membrane. All living cells maintain an active secretory pathway having several functions besides protein secretion. Proteins move between the various compartments of this pathway as cargo in vesicles. All proteins that have a signal peptideare translated on rough ER and enter the secretory pathway via translocation into the ER lumen. Correct folding is necessary not only for proper protein function but also for transport. Proteins that are not correctly folded are degraded in the ER. Vesicle formation and sorting are complex processes that involve integral membrane proteins (e.g., receptors) and cytosolic proteins (e.g., vesicle coat proteins). Coat formation is necessary for vesicle budding. Vesicles always uncoat before fusing with their target compartments Cells make extensive use of highly regulated GTP-binding proteins/GTPases to regulate and provide energy for secretory pathway activity. The secretory pathway targets proteins to the ER, Golgi, TGN, prevacuolar compartment, vacuole, and plasma membrane. Cells also have a vesicle-mediated mechanism for taking up proteins from their surroundings and delivering them to various compartments.

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