Browsing Department of Pathology: Faculty Research and Presentations by Authors
Consensus nomenclature for the human ArfGAP domain-containing proteinsKahn, Richard A.; Bruford, Elspeth; Inoue, Hiroki; Logsdon, John M.; Nie, Zhongzhen; Premont, Richard T.; Randazzo, Paul A.; Satake, Masanobu; Theibert, Anne B.; Zapp, Maria L.; et al. (2008-09-22)At the FASEB summer research conference on â Arf Family GTPasesâ , held in Il Ciocco, Italy in June, 2007, it became evident to researchers that our understanding of the family of Arf GTPase activating proteins (ArfGAPs) has grown exponentially in recent years. A common nomenclature for these genes and proteins will facilitate discovery of biological functions and possible connections to pathogenesis. Nearly 100 researchers were contacted to generate a consensus nomenclature for human ArfGAPs. This article describes the resulting consensus nomenclature and provides a brief description of each of the 10 subfamilies of 31 human genes encoding proteins containing the ArfGAP domain.
Dynamin2- and endothelial nitric oxide synthaseâ regulated invasion of bladder epithelial cells by uropathogenic Escherichia coliWang, Zhimin; Humphrey, Ceba; Frilot, Nicole; Wang, Gaofeng; Nie, Zhongzhen; Moniri, Nader H.; Daaka, Yehia; Department of Pathology (2011-01-10)Invasion of bladder epithelial cells by uropathogenic Escherichia coli (UPEC) contributes to antibiotic-resistant and recurrent urinary tract infections (UTIs), but this process is incompletely understood. In this paper, we provide evidence that the large guanosine triphosphatase dynamin2 and its partner, endothelial nitric oxide (NO) synthase (NOS [eNOS]), mediate bacterial entry. Overexpression of dynamin2 or treatment with the NO donor S-nitrosothiols increases, whereas targeted reduction of endogenous dynamin2 or eNOS expression with ribonucleic acid interference impairs, bacterial invasion. Exposure of mouse bladder to small molecule NOS inhibitors abrogates infection of the uroepithelium by E. coli, and, concordantly, bacteria more efficiently invade uroepithelia isolated from wild-type compared with eNOSâ /â mice. E. coli internalization promotes rapid phosphorylation of host cell eNOS and NO generation, and dynamin2 S-nitrosylation, a posttranslational modification required for the bacterial entry, also increases during E. coli invasion. These findings suggest that UPEC escape urinary flushing and immune cell surveillance by means of eNOS-dependent dynamin2 S-nitrosylation and invasion of host cells to cause recurrent UTIs.