Myosin V1 regulates endocytosis of the cystic fibrosis transmembrane conductance regulator

Agnieszka Swiatecka-Urban, Cary Boydi, Bonita Coutermarsh, Katherine H. Karlson, Roxanna Barnaby, Laura Aschenbrenner, George M. Langford, Tama Hasson, Brace A. Stanton

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated Cl- channel expressed in the apical plasma membrane in fluid-transporting epithelia. Although CFTR is rapidly endocytosed from the apical membrane of polarized epithelial cells and efficiently recycled back to the plasma membrane, little is known about the molecular mechanisms regulating CFTR endocytosis and endocytic recycling. Myosin VI, an actin-dependent, minus-end directed mechano1 enzyme, has been implicated in clathrin-mediated endocytosis in epithelial cells. The goal of this study was to determine whether myosin VI regulates CFTR endocytosis. Endogenous, apical membrane CFTR in polarized human airway epithelial cells (Calu-3) formed a complex with myosin VI, the myosin VI adaptor protein Disabled 2 (Dab2), and clathrin. The tail domain of myosin VI, a dominant-negative recombinant fragment, displaced endogenous myosin VI from interacting with Dab2 and CFTR and increased the expression of CFTR in the plasma membrane by reducing CFTR endocytosis. However, the myosin VI tail fragment had no effect on the recycling of endocytosed CFTR or on fluid-phase endocytosis. CFTR endocytosis was decreased by cytochalasin D, an actin-filament depolymerizing agent. Taken together, these data indicate that myosin VI and Dab2 facilitate CFTR endocytosis by a mechanism that requires actin filaments.

Original languageEnglish (US)
Pages (from-to)38025-38031
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number36
DOIs
StatePublished - Sep 3 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Swiatecka-Urban, A., Boydi, C., Coutermarsh, B., Karlson, K. H., Barnaby, R., Aschenbrenner, L., Langford, G. M., Hasson, T., & Stanton, B. A. (2004). Myosin V1 regulates endocytosis of the cystic fibrosis transmembrane conductance regulator. Journal of Biological Chemistry, 279(36), 38025-38031. https://doi.org/10.1074/jbc.M403141200