Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.

ABSTRACT: 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 G? subunit EhG?1 exhibits conventional nucleotide cycling properties and is seen to interact with EhG?? dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhG?1 highlights unique features and classification outside of conventional mammalian G? subfamilies. E. histolytica trophozoites overexpressing wildtype EhG?1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhG?1-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 EhG?1 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.

SUBMITTER: Bosch DE 

PROVIDER: S-EPMC3499586 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature