Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells

Agnieszka Swiatecka-Urban, Laleh Talebian, Eiko Kanno, Sophie Moreau-Marquis, Bonita Coutermarsh, Karyn Hansen, Katherine H. Karlson, Roxanna Barnaby, Richard E. Cheney, George M. Langford, Mitsunori Fukuda, Bruce A. Stanton

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl - secretion across fluid-transporting epithelia is regulated, in part, by modulating the number of CFTR Cl- channels in the plasma membrane by adjusting CFTR endocytosis and recycling. However, the mechanisms that regulate CFTR recycling in airway epithelial cells remain unknown, at least in part, because the recycling itineraries of CFTR in these cells are incompletely understood. In a previous study, we demonstrated that CFTR undergoes trafficking in Rab11a-specific apical recycling endosomes in human airway epithelial cells. Myosin Vb is a plus-end-directed, actin-based mechanoenzyme that facilitates protein trafficking in Rab11a-specific recycling vesicles in several cell model systems. There are no published studies examining the role of myosin Vb in airway epithelial cells. Thus, the goal of this study was to determine whether myosin Vb facilitates CFTR recycling in polarized human airway epithelial cells. Endogenous CFTR formed a complex with endogenous myosin Vb and Rab11a. Silencing myosin Vb by RNA mediated interference decreased the expression of wild-type CFTR and ΔF508-CFTR in the apical membrane and decreased CFTR-mediated Cl- secretion across polarized human airway epithelial cells. A recombinant tail domain fragment of myosin Vb attenuated the plasma membrane expression of CFTR by arresting CFTR recycling. The dominant-negative effect was dependent on the ability of the myosin Vb tail fragment to interact with Rab11a. Taken together, these data indicate that myosin Vb is required for CFTR recycling in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells.

Original languageEnglish (US)
Pages (from-to)23725-23736
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number32
DOIs
StatePublished - Aug 10 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Swiatecka-Urban, A., Talebian, L., Kanno, E., Moreau-Marquis, S., Coutermarsh, B., Hansen, K., Karlson, K. H., Barnaby, R., Cheney, R. E., Langford, G. M., Fukuda, M., & Stanton, B. A. (2007). Myosin Vb is required for trafficking of the cystic fibrosis transmembrane conductance regulator in Rab11a-specific apical recycling endosomes in polarized human airway epithelial cells. Journal of Biological Chemistry, 282(32), 23725-23736. https://doi.org/10.1074/jbc.M608531200