Endosome acidification and receptor trafficking: bafilomycin A1 slows receptor externalization by a mechanism involving the receptor's internalization motif.

  • Harter C
  • Mellman I
  • Johnson L
 et al. 
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Abstract

To examine the relationship between endosome acidification and receptor trafficking, transferrin receptor trafficking was characterized in Chinese hamster ovary cells in which endosome acidification was blocked by treatment with the specific inhibitor of the vacuolar H(+)-ATPase, bafilomycin A1. Elevating endosome pH slowed the receptor externalization rate to approximately one-half of control but did not affect receptor internalization kinetics. The slowed receptor externalization required the receptor's cytoplasmic domain and was largely eliminated by substitutions replacing either of two aromatic amino acids within the receptor's cytoplasmic YTRF internalization motif. These results confirm, using a specific inhibitor of the vacuolar proton pump, that proper endosome acidification is necessary to maintain rapid recycling of intracellular receptors back to the plasma membrane. Moreover, receptor return to the plasma membrane is slowed in the absence of proper endosome acidification by a signal-dependent mechanism involving the receptor's cytoplasmic tyrosine-containing internalization motif. These results, in conjunction with results from other studies, suggest that the mechanism for clustering receptors in plasma membrane clathrin-coated pits may be an example of a more general mechanism that determines the dynamic distribution of membrane proteins among various compartments with luminal acidification playing a crucial role in this process.

Author-supplied keywords

  • Absolute quantification
  • Adaptor Protein Complex 2
  • Adaptor Protein Complex 2: immunology
  • Adaptor Proteins
  • Adenosine Triphosphatases
  • Adenosine Triphosphatases: metabolism
  • Amino Acid Sequence
  • Ammonia
  • Ammonia: pharmacology
  • Ammonium Chloride
  • Ammonium Chloride: pharmacology
  • Androstenes
  • Androstenes: pharmacology
  • Animals
  • Anti-Bacterial Agents
  • Anti-Bacterial Agents: pharmacology
  • Antigen Presentation
  • Antigen Presentation: immunology
  • Antigens
  • Antimalarials
  • Antimalarials: pharmacology
  • Apoptosis
  • Biological Markers
  • Biological Transport
  • Biological Transport: drug effects
  • CD
  • CHO Cells
  • COS Cells
  • Calibration
  • Calmodulin
  • Calmodulin: metabolism
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone: pharmac
  • Cell Adhesion Molecules
  • Cell Dedifferentiation
  • Cell Dedifferentiation: immunology
  • Cell Line
  • Cell Membrane
  • Cell Membrane: drug effects
  • Cell Membrane: metabolism
  • Cell biology
  • Cells
  • Cercopithecus aethiops
  • Chloroquine
  • Chloroquine: pharmacology
  • Clathrin
  • Clathrin: metabolism
  • Cricetinae
  • Cricetulus
  • Cultured
  • Dendritic Cells
  • Dendritic Cells: cytology
  • Dendritic Cells: immunology
  • Dextrans
  • Dextrans: analogs & derivatives
  • Endocytosis
  • Endocytosis: drug effects
  • Endocytosis: physiology
  • Endoplasmic Reticulum
  • Endoplasmic Reticulum: ultrastructure
  • Endosome isolation
  • Endosomes
  • Endosomes: drug effects
  • Endosomes: immunology
  • Endosomes: metabolism
  • Endosomes: physiology
  • Enzyme Inhibitors
  • Enzyme Inhibitors: pharmacology
  • Epidermal Growth Factor
  • Epidermal Growth Factor: metabolism
  • Epitopes
  • Erythrocytes
  • Erythrocytes: parasitology
  • Flow Cytometry
  • Fluorescein
  • Fluoresceins
  • Fluorescence
  • Fluorescence: methods
  • GPI-Linked Proteins
  • GRB2 Adaptor Protein
  • GRB2 Adaptor Protein: metabolism
  • Golgi Apparatus
  • Golgi Apparatus: drug effects
  • Golgi Apparatus: metabolism
  • Golgi Apparatus: ultrastructure
  • Green Fluorescent Proteins
  • Guanine Nucleotide Exchange Factors
  • Guanine Nucleotide Exchange Factors: genetics
  • Guanine Nucleotide Exchange Factors: metabolism
  • HLA-DR Antigens
  • HLA-DR Antigens: immunology
  • Hela Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Insulin
  • Insulin: metabolism
  • Interferon-alpha
  • Interferon-alpha: biosynthesis
  • Intracellular Fluid
  • Intracellular Fluid: chemistry
  • Intracellular Membranes
  • Intracellular Membranes: metabolism
  • Kinetics
  • Ligands
  • Liposomes
  • Liposomes: metabolism
  • Liver
  • Liver: chemistry
  • Liver: metabolism
  • Luminescent Proteins
  • Luminescent Proteins: biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Activation: immunology
  • Lysosomal-Associated Membrane Protein 1
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes
  • Lysosomes: drug effects
  • Lysosomes: metabolism
  • Lysosomes: physiology
  • MAP kinase
  • Macrolides
  • Macrolides: pharmacology
  • Macrophages
  • Macrophages: physiology
  • Macrophages: ultrastructure
  • Magnetic beads
  • Matrix-assisted laser desorption/ionization-time-o
  • Mefloquine
  • Melanoma
  • Melanoma: immunology
  • Melanosomes
  • Melanosomes: immunology
  • Membrane Glycoproteins
  • Membrane Glycoproteins: immunology
  • Membrane Glycoproteins: metabolism
  • Membrane fusion
  • Mice
  • Microscopy
  • Microtubules
  • Microtubules: chemistry
  • Microtubules: metabolism
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 1: metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 3: metabolism
  • Molecular Motor Proteins
  • Molecular Motor Proteins: metabolism
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation
  • Neoplasm
  • Neoplasm: immunology
  • Nerve Tissue Proteins
  • Nerve Tissue Proteins: metabolism
  • Neuronal
  • Neuronal: immunology
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides
  • Oligodeoxyribonucleotides: chemistry
  • Oligodeoxyribonucleotides: immunology
  • Organelle proteomics
  • Organelles
  • Organelles: metabolism
  • Organoids
  • Organoids: drug effects
  • Organoids: physiology
  • Phagocytosis
  • Phagosome
  • Phosphoproteins
  • Phosphoproteins: metabolism
  • Phosphorylation
  • Plasmodium falciparum
  • Plasmodium falciparum: drug effects
  • Plasmodium falciparum: ultrastructure
  • Point Mutation
  • Polymerase Chain Reaction
  • Protein Kinase C
  • Protein Kinase C: metabolism
  • Protein Structure
  • Protein Transport
  • Protein Transport: immunology
  • Proteome
  • Proteome: analysis
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins c-raf: metabolism
  • Proton-Translocating ATPases
  • Proton-Translocating ATPases: antagonists & inhibi
  • Quinine
  • Quinine: pharmacology
  • Quinolines
  • Quinolines: pharmacology
  • RNA
  • Rats
  • Receptors
  • Recombinant Fusion Proteins
  • Recombinant Fusion Proteins: metabolism
  • Recombinant Proteins
  • Recombinant Proteins: biosynthesis
  • Recombinant Proteins: metabolism
  • Rho Guanine Nucleotide Exchange Factors
  • Rhodamines
  • Scaffold complex
  • Signal Transduction
  • Signal Transduction: drug effects
  • Signaling endosomes
  • Site-Directed
  • Small Interfering
  • Small Interfering: genetics
  • Small Interfering: immunology
  • Small Interfering: metabolism
  • Spectrometry
  • Subcellular fractionation
  • T-Lymphocyte
  • T-Lymphocyte: immunology
  • T-Lymphocytes
  • T-Lymphocytes: cytology
  • T-Lymphocytes: immunology
  • Tertiary
  • Time Factors
  • Toll-Like Receptor 9
  • Toll-Like Receptor 9: immunology
  • Toll-Like Receptor 9: metabolism
  • Transfection
  • Transferrin
  • Transferrin: chemistry
  • Transferrin: drug effects
  • Transferrin: metabolism
  • Transport Vesicles
  • Transport Vesicles: chemistry
  • Transport Vesicles: metabolism
  • Tumor
  • Vacuolar Proton-Translocating ATPases
  • Vacuoles
  • Vacuoles: metabolism
  • Vero Cells
  • Vesicular Transport
  • beta Karyopherins
  • beta Karyopherins: genetics
  • beta Karyopherins: metabolism
  • colocalization
  • disease
  • electric field
  • electroporation
  • endocytosis
  • endosomal trafficking
  • endosomes
  • fluorescence in situ hybridization
  • gene electrotransfer
  • golgi
  • gp100 Melanoma Antigen
  • herpesvirus
  • human herpesvirus 6
  • immunoisolation
  • integration
  • lymphoblastoid cell lines
  • macrophage
  • marek
  • metaphase spread
  • nanoparticles
  • plasmid DNA
  • rab1 GTP-Binding Proteins
  • rab1 GTP-Binding Proteins: genetics
  • rab1 GTP-Binding Proteins: metabolism
  • ras Proteins
  • ras Proteins: genetics
  • ras Proteins: metabolism
  • s disease virus
  • single-particle tracking
  • subcellular traf fi cking
  • telomere
  • telomeric repeats
  • traffic

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Authors

  • C Harter

  • I Mellman

  • L S Johnson

  • K W Dunn

  • B Pytowski

  • T E McGraw

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