Regulation of endocytic trafficking and acidification are independent of the cystic fibrosis transmembrane regulator

Kenneth Dunn, Juliet Park, Carol E. Semrad, Dana L. Gelman, Tracy Shevell, Timothy E. McGraw

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Cystic fibrosis is associated with mutations of the cystic fibrosis transmembrane regulator (CFTR), a cAMP-regulated plasma membrane Cl- channel. Mutations in the CFTR have been reported to not only impair Cl- transport at the plasma membrane but also inhibit organelle acidification and disrupt cAMP-regulated plasma membrane recycling. Comparisons of cultured pancreatic adenocarcinoma cells expressing the Δ508 mutant CFTR (CFPAC-1 cells) with genetically matched CFPAC-1 cells transfected with the wild-type CFTR demonstrate that expression of wild-type CFTR restores cAMP-mediated plasma membrane Cl- transport, but has not effect on pH regulation of endosomes labeled with either transferrin or wheat germ agglutinin. Endosome pH was, in all cases, similar in the two cell lines and unaffected by treatment with the cAMP agonist forskolin. Forskolin treatment had no effect on transferrin internalization, but increased recycling by 30-40% in both cell lines. The kinetics of wheat germ agglutinin recycling were negligibly affected by forskolin in either cell line. These results demonstrate that endocytic acidification and cAMP-mediated endocytic protein redistribution are similar in genetically matched CFPAC-1 cells which differ only in the expression of mutant or wild-type CFTR.

Original languageEnglish (US)
Pages (from-to)5336-5345
Number of pages10
JournalJournal of Biological Chemistry
Volume269
Issue number7
StatePublished - Feb 18 1994
Externally publishedYes

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Acidification
Cell membranes
Cystic Fibrosis
Colforsin
Cells
Recycling
Wheat Germ Agglutinins
Transferrin
Cell Membrane
Endosomes
Cell Line
Mutation
Kinetics
Ion Channels
Organelles
Adenocarcinoma
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of endocytic trafficking and acidification are independent of the cystic fibrosis transmembrane regulator. / Dunn, Kenneth; Park, Juliet; Semrad, Carol E.; Gelman, Dana L.; Shevell, Tracy; McGraw, Timothy E.

In: Journal of Biological Chemistry, Vol. 269, No. 7, 18.02.1994, p. 5336-5345.

Research output: Contribution to journalArticle

Dunn, Kenneth ; Park, Juliet ; Semrad, Carol E. ; Gelman, Dana L. ; Shevell, Tracy ; McGraw, Timothy E. / Regulation of endocytic trafficking and acidification are independent of the cystic fibrosis transmembrane regulator. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 7. pp. 5336-5345.
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