Harpers

INTRACELLULAR TRAFFIC & SORTING OF PROTEINS / 513Various Disorders Result From Mutationsin Genes Encoding Proteins Involvedin Intracellular TransportSome of these are listed in Table 46–9; the majority affectlysosomal function. A number of other mutationsaffecting intracellular protein transport have been reportedbut are not included here.SUMMARY• Many proteins are targeted to their destinations bysignal sequences. A major sorting decision is madewhen proteins are partitioned between cytosolic andmembrane-bound polyribosomes by virtue of the absenceor presence of a signal peptide.• The pathways of protein import into mitochondria,nuclei, peroxisomes, and the endoplasmic reticulumare described.• Many proteins synthesized on membrane-boundpolyribosomes proceed to the Golgi apparatus andthe plasma membrane in transport vesicles.• A number of glycosylation reactions occur in compartmentsof the Golgi, and proteins are furthersorted in the trans-Golgi network.• Most proteins destined for the plasma membraneand for secretion appear to lack specific signals—adefault mechanism.• The role of chaperone proteins in the folding of proteinsis presented, and a model describing buddingand attachment of transport vesicles to a target membraneis summarized.• Membrane assembly is discussed and shown to becomplex. Asymmetry of both lipids and proteins ismaintained during membrane assembly.• A number of disorders have been shown to be due tomutations in genes encoding proteins involved invarious aspects of protein traffic and sorting.REFERENCESFuller GM, Shields DL: Molecular Basis of Medical Cell Biology.McGraw-Hill, 1998.Gould SJ et al: The peroxisome biogenesis disorders. In: The Metabolicand Molecular Bases of Inherited Disease, 8th ed. ScriverCR et al (editors). McGraw-Hill, 2001.Graham JM, Higgins JA: Membrane Analysis. BIOS Scientific,1997.Griffith J, Sansom C: The Transporter Facts Book. Academic Press,1998.Lodish H et al: Molecular Cell Biology, 4th ed. Freeman, 2000.(Chapter 17 contains comprehensive coverage of protein sortingand organelle biogenesis.)Olkkonen VM, Ikonen E: Genetic defects of intracellular-membranetransport. N Engl J Med 2000;343:1095.Reithmeier RAF: Assembly of proteins into membranes. In: Biochemistryof Lipids, Lipoproteins and Membranes. Vance DE,Vance JE (editors). Elsevier, 1996.Sabatini DD, Adesnik MB: The biogenesis of membranes and organelles.In: The Metabolic and Molecular Bases of InheritedDisease, 8th ed. Scriver CR et al (editors). McGraw-Hill,2001.