Bacteria-Induced Uroplakin Signaling Mediates Bladder Response to Infection

PLoS Pathogens

Ruth E. Berry¹  Praveen Thumbikat¹  Anthony J. Schaeffer¹  Benjamin K. Billips¹  David J. Klumpp¹  Tetiana Zaichuk¹  Ryan E. Yaggie¹  Tung-Tien Sun²  Ge Zhou² 

[1] Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America;Departments of Cell Biology, Dermatology, Pharmacology and Urology, New York University School of Medicine, New York, New York, United States of America

关键词: Apoptosis;    Bladder;    Phosphorylation;    Calcium signaling;    Cell staining;    Immunoprecipitation;    Pathogenesis;    Fluorescence imaging;   

DOI  :  10.1371/journal.ppat.1000415

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Urinary tract infections are the second most common infectious disease in humans and are predominantly caused by uropathogenic E. coli (UPEC). A majority of UPEC isolates express the type 1 pilus adhesin, FimH, and cell culture and murine studies demonstrate that FimH is involved in invasion and apoptosis of urothelial cells. FimH initiates bladder pathology by binding to the uroplakin receptor complex, but the subsequent events mediating pathogenesis have not been fully characterized. We report a hitherto undiscovered signaling role for the UPIIIa protein, the only major uroplakin with a potential cytoplasmic signaling domain, in bacterial invasion and apoptosis. In response to FimH adhesin binding, the UPIIIa cytoplasmic tail undergoes phosphorylation on a specific threonine residue by casein kinase II, followed by an elevation of intracellular calcium. Pharmacological inhibition of these signaling events abrogates bacterial invasion and urothelial apoptosis in vitro and in vivo. Our studies suggest that bacteria-induced UPIIIa signaling is a critical mediator of bladder responses to insult by uropathogenic E. coli.

【 授权许可】

CC BY