Summary: Molecular Biology of the Cell
Vol. 18, 13121323, April 2007
Apical Epidermal Growth Factor Receptor Signaling:
Regulation of Stretch-dependent Exocytosis in Bladder
Elena M. Balestreire and Gerard Apodaca
Laboratory of Epithelial Cell Biology, Departments of Medicine and Cell Biology and Physiology, University
of Pittsburgh, Pittsburgh, PA 15261
Submitted September 21, 2006; Revised January 18, 2007; Accepted January 29, 2007
Monitoring Editor: Keith Mostov
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.