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Endocytosis ,959 Annual Reviews www.annualreviews.org/aronline Ann.Rev. Biochem.197Z 46.’669-722 Copyright©1977 by AnnualReviews Inc. All rights reserved ENDOCYTOSIS ,959 Samuel2 C. Silverstein, 1 Ralph M. Steinman, and Zanvi1,4. Cohn Department of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10023 CONTENTS PERSPECTIVESANDSUMMARY .......................................................................... 670 INTRODUCTION........................................................................................................ 673 Typesof Endocytosis............................................................................................ 673 Morphologyof Endocytic Vacuoles .................................................................. 674 Fateof EndocyticVacuoles ................................................................................ 676 QUANTITATIONOF PARTICLE AND SOLUTE UPTAKE .............................. 678 Phagocytosisof Large Particles .......................................................................... 678 t’inocytosisof Solutesand Fluid ........................................................................ 679 ENERGYREQUIREMENTS FORENDOCYTOSIS .............................................. 681 Temperature.......................................................................................................... 682 ATP.......................................................................................................................... 683 CYTOPLASMICCONTRACTILE ELEMENTS ...................................................... 685 Microtubules.......................................................................................................... 685 Actomyosin.............................................................................................................. 686 Phagocytosis........................................................................................................ 686 Pinocytosis.......................................................................................................... 689 by Rockefeller University on 08/15/07. For personal use only. FACTORSREGULATING PHAGOCYTOSIS ........................................................ 689 SurfaceProperties of the Particle ...................................................................... 689 lmmunoglobulins................................................................................................ 690 Complement........................................................................................................ 691 Annu. Rev. Biochem. 1977.46:669-722. Downloaded from arjournals.annualreviews.org SurfaceProperties of thePhagocyte .................................................................. 692 Fcreceptors ........................................................................................................ 692 Trypsin-resistantFcreceptors ............................................................................ 692 Trypsin-sensitiveFcreceptors .............................................................................. 693 C3receptors ........................................................................................................ 694 "Nonspecificreceptors". ....................................................................................... 695 Attachmentof Particlesto the Phagocyte’sSurface ...................................... 696 1Samuel C. Silverstein is an Established Investigator of The American Heart Association. 2Ralph M. Steinman is a Leukemia Society of America Scholar and an Irma T. Hirschl Fellow. 669 Annual Reviews www.annualreviews.org/aronline 670 SILVERSTEIN, STEINMAN & COHN Segmental Responseof the Cell Surface to a Phagocytic Stimulus .......... 696 Rolesof Ligandsand Receptors in ParticleIngestion .................................. 697 MembraneRemodeling and Fusion DuringPhagocytosis .......................... 699 METABOLICCONSEQUENCES OFPHAGOCYTOSIS ........................................ 700 OxidativeMetabolism .......................................................................................... 700 PhospholipidsandCholesterol ............................................................................ 701 Secretionof Neutraland Acid Hydrolases ...................................................... 701 Inductionof Lysosomal-EnzymeSynthesis ...................................................... 702 CyclicNucleotides ................................................................................................ 702 FACTORSREGULATING PINOCYTOSIS .............................................................. 703 Pinocytosisof LigandsBound to the Cell Surface........................................ 703 PinocytosisFollowing Secretion .......................................................................... 704 "Constitutive"Pinocytosis .................................................................................... 704 MEMBRANEFLOWDURING ENDOCYTOSIS .................................................... 705 Rate of Plasma-MembraneInflux--Morphologic Studies .......................... 705 Fate of the lnteriorized Plasma Membrane--MorphologicStudies .......... 706 Fusionwith lysosomes ........................................................................................ 706 Recycling............................................................................................................ 707 Composition of the lnteriorized Plasma Membrane--Biochemical Studies.................................................................................................... 708 Enzymes.............................................................................................................. 709 Polypeptides........................................................................................................ 709 Lipids.................................................................................................................. 710 Fate of the Interiorized Plasma MembraneBiochemical Studies .......... 710 Endocytosisand Plasma-Membrane Turnover .............................................. 710 Turnoverof bulk radiolabel .............................................................................. 710 Turnoverof individual components .................................................................... 711 ENDOCYTOSISAND THE PENETRATION OF INTRACELLULAR PARASITES................................................................................................ 711 AgentsThat Enter the CytoplasmicMatrix .................................................... 712 AgentsThat Replicate Within Lysosomes ...................................................... 712 AgentsThat Replicate Within Phagosomes .................................................... 712 ENDOCYTOSISANDHOMEOSTASIS .................................................................... 713 SPECULATIONS.......................................................................................................... 714 by Rockefeller University on 08/15/07. For personal use only. Nutrition................................................................................................................ 714 Controlof Metabolism ........................................................................................ 714 TheCell Surface .................................................................................................. 715 Therapy.................................................................................................................. 715 Annu. Rev. Biochem. 1977.46:669-722. Downloaded from arjournals.annualreviews.org Liposomes............................................................................................................ 715 Conjugatesof intercalating drugs with DNA .................................................... 715 Polycationization................................................................................................ 716 Alterationof oligosaccharides ............................................................................ 716 Entryof macromoleculesinto the cytoplasmicmatrix ...................................... 716 PERSPECTIVES AND SUMMARY Endoeytosis is a widespread cellular function that regulates the quantal uptake of exogenous molecules from the cell’s environment via plasma- membrane-derived vesicles and vacuoles. Both soluble (pinocytosis) and Annual Reviews www.annualreviews.org/aronline ENDOCYTOSIS 671 particulate (phagocytosis) substances maybe interiorized, destined either for the vacuolar apparatus and intracellular digestion or transport through the cytoplasm and subsequent exocytosis. Although most, if not all, eukar- yotic cells demonstrate these primitive functions, they are particularly prominent in leucocytes, macrophages, capillary endothelial and thyroid epithelial cells, yolk sac, and oocytes. Here they are involved in host de- fense, immunological reactions, macromolecular transport, hormonetrans- formations, and the regulation of metabolic pathways, and perhaps in cellular nutrition as well. Manycells generate pinocytic vesicles at constant but different rates, enclosing fluid and solutes at the concentration at which they are found in the extracellular milieu. Those solutes that bind to the plasma membrane are interiorized by adsorptive pinocytosis at rates often manythousandfold above the uptake of fluid-phase reactants. In someinstances the interaction of a multivalent ligand, such as concanavalin A, with the plasma membrane
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