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Vol. 18, Issue 4, 1312-1323, April 2007

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Apical Epidermal Growth Factor Receptor Signaling: Regulation of Stretch-dependent Exocytosis in Bladder Umbrella Cells

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.

Address correspondence to: Gerard Apodaca (gla6{at}pitt.edu)

Abbreviations used: BFA, brefeldin A; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; HB-EGF, heparin-binding epidermal growth factor-like protein.

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