Apical epidermal growth factor receptor signaling: regulation of stretch-dependent exocytosis in bladder umbrella cells.
The apical surface of polarized epithelial cells receives input from mediators, growth factors, and mechanical stimuli. How these stimuli are coordinated to regulate complex cellular functions such as polarized membrane traffic is not understood. We analyzed the requirement for growth factor signaling and mechanical stimuli in umbrella cells, which line the mucosal surface of the bladder and dynamically insert and remove apical membrane in response to stretch. We observed that stretch-stimulated exocytosis required apical epidermal growth factor (EGF) receptor activation and that activation occurred in an autocrine manner downstream of heparin-binding EGF-like growth factor precursor cleavage. Long-term changes in apical exocytosis depended on protein synthesis, which occurred upon EGF receptor-dependent activation of mitogen-activated protein kinase signaling. Our results indicate a novel physiological role for the EGF receptor that couples upstream mechanical stimuli to downstream apical EGF receptor activation that may regulate apical surface area changes during bladder filling.
Balestreire
Elena M
EM
Laboratory of Epithelial Cell Biology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Apodaca
Gerard
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000276:immunology / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003513:Cycloheximide; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D006023:Glycoproteins; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; D014443:Tyrosine; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; C483804:Erbb2 protein, rat