Journal article
Segregation of receptor and ligand regulates activation of epithelial growth factor receptor
Nature (London), Vol.422(6929), pp.322-326
2003
DOI: 10.1038/nature01440
PMID: 12646923
Abstract
Interactions between ligands and receptors are central to communication between cells and tissues. Human airway epithelia constitutively produce both a ligand, the growth factor heregulin, and its receptors—erbB2, erbB3 and erbB4 (refs 1–3). Although heregulin binding initiates cellular proliferation and differentiation4,5,6,7, airway epithelia have a low rate of cell division8. This raises the question of how ligand–receptor interactions are controlled in epithelia. Here we show that in differentiated human airway epithelia, heregulin-α is present exclusively in the apical membrane and the overlying airway surface liquid, physically separated from erbB2–4, which segregate to the basolateral membrane. This physical arrangement creates a ligand–receptor pair poised for activation whenever epithelial integrity is disrupted. Indeed, immediately following a mechanical injury, heregulin-α activates erbB2 in cells at the edge of the wound, and this process hastens restoration of epithelial integrity. Likewise, when epithelial cells are not separated into apical and basolateral membranes (‘polarized’), or when tight junctions between adjacent cells are opened, heregulin-α activates its receptor. This mechanism of ligand–receptor segregation on either side of epithelial tight junctions may be vital for rapid restoration of integrity following injury, and hence critical for survival. This model also suggests a mechanism for abnormal receptor activation in diseases with increased epithelial permeability.
Details
- Title: Subtitle
- Segregation of receptor and ligand regulates activation of epithelial growth factor receptor
- Creators
- Paola D VERMEER - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United StatesLisa A EINWALTER - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United StatesThomas O MONINGER - Central Microscopy Research Facility, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United StatesTatiana ROKHLINA - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United StatesJeffrey A KERN - University Hospitals of Cleveland, 11100 Euclid Avenue, 610 Wearn, LKSD 5067, Cleveland, Ohio 44106, United StatesJoseph ZABNER - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United StatesMichael J WELSH - Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.422(6929), pp.322-326
- Publisher
- Nature Publishing; London
- DOI
- 10.1038/nature01440
- PMID
- 12646923
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 2003
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020795002771
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