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Publication Abstract from PubMed

Heterotrimeric G-protein signaling pathways are vital components of physiology, and many are amenable to pharmacologic manipulation. Here, we identify functional heterotrimeric G-protein subunits in Entamoeba histolytica, the causative agent of amoebic colitis. The E. histolytica Galpha subunit EhGalpha1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGbetagamma dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGalpha1 highlights unique features and classification outside of conventional mammalian Galpha subfamilies. E. histolytica trophozoites overexpressing wildtype EhGalpha1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGalpha1-overexpressing trophozoites also display enhanced transmigration across a Matrigel barrier, an effect that may result from altered baseline migration. Inducible expression of a dominant negative EhGalpha1 variant engenders the converse phenotypes. Transcriptomic studies reveal that modulation of pathogenesis-related trophozoite behaviors by perturbed heterotrimeric G-protein expression includes transcriptional regulation of virulence factors and altered trafficking of cysteine proteases. Collectively, our studies suggest that E. histolytica possesses a divergent heterotrimeric G-protein signaling axis that modulates key aspects of cellular processes related to the pathogenesis of this infectious organism.

Heterotrimeric G-protein Signaling Is Critical to Pathogenic Processes in Entamoeba histolytica.,Bosch DE, Kimple AJ, Muller RE, Giguere PM, Machius M, Willard FS, Temple BR, Siderovski DP PLoS Pathog. 2012 Nov;8(11):e1003040. doi: 10.1371/journal.ppat.1003040. Epub, 2012 Nov 15. PMID:23166501^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.