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First published online November 18, 2003
doi: 10.1242/10.1242/jcs.00830
Research Article |
1 Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
2 Department of Cell Biology and Anatomy, University of California, Davis, CA 95616 USA
3 Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA
4 Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA
* Author for correspondence (e-mail: brodys{at}msnotes.wustl.edu)
Accepted 13 August 2003
Establishment and maintenance of epithelial cell polarity depend on cytoskeletal organization and protein trafficking to polarized cortical membranes. ERM (ezrin, radixin, moesin) family members link polarized proteins with cytoskeletal actin. Although ERMs are often considered to be functionally similar, we found that, in airway epithelial cells, apical localization of ERMs depend on cell differentiation and is independently regulated. Moesin was present in the apical membrane of all undifferentiated epithelial cells. However, in differentiated cells, ezrin and moesin were selectively localized to apical membranes of ciliated airway cells and were absent from secretory cells. To identify regulatory proteins required for selective ERM trafficking, we evaluated airway epithelial cells lacking Foxj1, an F-box factor that directs programs required for cilia formation at the apical membrane. Interestingly, Foxj1 expression was also required for localization of apical ezrin, but not moesin. Additionally, membrane-cytoskeletal and threonine-phosphorylated ezrin were decreased in Foxj1-null cells, consistent with absent apical ezrin. Although apical moesin expression was present in null cells, it could not compensate for ezrin because ERM-associated EBP50 and the ß2 adrenergic receptor failed to localize apically in the absence of Foxj1. These findings indicate that Foxj1 regulates ERM proteins differentially to selectively direct the apical localization of ezrin for the organization of multi-protein complexes in apical membranes of airway epithelial cells.
Key words: Cytoskeleton, Differentiation, Lung, Cilia, Mouse
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