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

Lester S. Johnson, Kenneth Dunn, Bronislaw Pytowski, Timothy E. McGraw

Research output: Contribution to journalArticle

158 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1251-1266
Number of pages16
JournalMolecular Biology of the Cell
Volume4
Issue number12
StatePublished - Dec 1993

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Endosomes
Cell Membrane
Cytoplasmic and Nuclear Receptors
Amino Acid Receptors
Vacuolar Proton-Translocating ATPases
Aromatic Amino Acids
Clathrin
Transferrin Receptors
Proton Pump Inhibitors
Cricetulus
Cluster Analysis
Ovary
Membrane Proteins
bafilomycin A1

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Endosome acidification and receptor trafficking : Bafilomycin A1 slows receptor externalization by a mechanism involving the receptor's internalization motif. / Johnson, Lester S.; Dunn, Kenneth; Pytowski, Bronislaw; McGraw, Timothy E.

In: Molecular Biology of the Cell, Vol. 4, No. 12, 12.1993, p. 1251-1266.

Research output: Contribution to journalArticle

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