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After studying this chapter, you should be able to:

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  • Know that many proteins are targeted by signal sequences to their correct destinations and that the Golgi apparatus plays an important role in sorting proteins.
  • Understand that specialized signals are involved in sorting proteins to mitochondria, the nucleus, and to peroxisomes.
  • Appreciate that N-terminal signal peptides play a key role in directing newly synthesized proteins into the lumen of the endoplasmic reticulum.
  • Know that chaperones prevent faulty folding of other proteins, that mechanisms exist for disposing of misfolded proteins, and that the endoplasmic reticulum acts as a quality control compartment.
  • Comprehend that ubiquitin is a key molecule in protein degradation.
  • Recognize the important role of transport vesicles in intracellular transport.
  • Appreciate that many diseases result from mutations in genes encoding proteins involved in intracellular transport and be familiar with the terms conformational diseases and diseases of proteostatic deficiency.

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Proteins must travel from polyribosomes, where they are synthesized, to many different sites in the cell to perform their particular functions. Some are destined to be components of specific organelles, others for the cytosol or for export, and yet others will be located in the various cellular membranes. Thus, there is considerable intracellular traffic of proteins. A major insight was the recognition by Blobel and subsequently others that for proteins to attain their proper locations, they generally contain information (a signal or coding sequence) that targets them appropriately. Once a number of the signals were defined (see Table 46–1), it became apparent that certain diseases result from mutations that affect these signals. In this chapter, we discuss the intracellular traffic of proteins and their sorting and briefly consider some of the disorders that result when abnormalities occur.

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Table Graphic Jump Location
Table 46–1 Some Sequences or Molecules that Direct Proteins to Specific Organelles
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The protein biosynthetic pathways in cells can be considered to be one large sorting system. Many proteins carry signals (usually but not always specific sequences of amino acids) that direct them to their destination, thus ensuring that they will end up in the appropriate membrane or cell compartment; these signals are a fundamental component of the sorting system. Usually, the signal sequences are recognized and interact with complementary areas of other proteins that serve as receptors for those containing the signals.

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A major sorting decision is made early in protein biosynthesis, when specific proteins are synthesized ...

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