Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator

John A. Picciano, Nadia Ameen, Barth Grant, Neil A. Bradbury

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Endocytic motifs in the carboxyl terminus of cystic fibrosis transmembrane conductance regulator (CFTR) direct internalization from the plasma membrane by clathrin-mediated endocytosis. However, the fate of such internalized CFTR has remained unknown. Internalized membrane proteins can be either targeted for degradation or recycled back to the plasma membrane. Using cell surface biotinylation and antibody uptake studies, we show that CFTR undergoes constitutive endocytosis and recycling back to the plasma membrane. Expression of dominant negative Rme-1 (a protein that regulates exit from the endosomal recycling compartment) in CFTR-expressing cells results in the expansion of recycling compartments. Transferrin, a marker for the endosomal recycling compartment, and CFTR accumulate in these enlarged recycling endosomes. Such accumulation leads to a loss of cell surface CFTR because it is prevented from being recycled back to the cell surface. In contrast, traffic of the low-density lipoprotein (LDL) is unaffected by the expression of dominant negative Rme-1. In addition, chimeras containing the extracellular domain of the transferrin receptor and the carboxyl terminal tail of CFTR also enter Rme-1-regulated recycling compartments and accumulate in these compartments containing dominant negative Rme-1, suggesting that in addition to endocytic signals, the carboxyl terminal tail of CFTR also contains intracellular traffic information.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number5 54-5
StatePublished - Nov 1 2003

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Recycling
Cell Membrane
Endocytosis
Biotinylation
Clathrin
Transferrin Receptors
Endosomes
Transferrin
LDL Lipoproteins
Membrane Proteins
Antibodies

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Keywords

  • Channel
  • Cystic fibrosis transmembrane conductance regulator
  • Endocytosis
  • Recycling
  • Rme-1

Cite this

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abstract = "Endocytic motifs in the carboxyl terminus of cystic fibrosis transmembrane conductance regulator (CFTR) direct internalization from the plasma membrane by clathrin-mediated endocytosis. However, the fate of such internalized CFTR has remained unknown. Internalized membrane proteins can be either targeted for degradation or recycled back to the plasma membrane. Using cell surface biotinylation and antibody uptake studies, we show that CFTR undergoes constitutive endocytosis and recycling back to the plasma membrane. Expression of dominant negative Rme-1 (a protein that regulates exit from the endosomal recycling compartment) in CFTR-expressing cells results in the expansion of recycling compartments. Transferrin, a marker for the endosomal recycling compartment, and CFTR accumulate in these enlarged recycling endosomes. Such accumulation leads to a loss of cell surface CFTR because it is prevented from being recycled back to the cell surface. In contrast, traffic of the low-density lipoprotein (LDL) is unaffected by the expression of dominant negative Rme-1. In addition, chimeras containing the extracellular domain of the transferrin receptor and the carboxyl terminal tail of CFTR also enter Rme-1-regulated recycling compartments and accumulate in these compartments containing dominant negative Rme-1, suggesting that in addition to endocytic signals, the carboxyl terminal tail of CFTR also contains intracellular traffic information.",
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Rme-1 regulates the recycling of the cystic fibrosis transmembrane conductance regulator. / Picciano, John A.; Ameen, Nadia; Grant, Barth; Bradbury, Neil A.

In: American Journal of Physiology - Cell Physiology, Vol. 285, No. 5 54-5, 01.11.2003.

Research output: Contribution to journalArticle

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AU - Bradbury, Neil A.

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