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

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 Gα subunit EhGα1 ex...

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Autores principales:	Dustin E Bosch, Adam J Kimple, Robin E Muller, Patrick M Giguère, Mischa Machius, Francis S Willard, Brenda R S Temple, David P Siderovski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4362270682cc4067a9e0e1c85c876670
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spelling	oai:doaj.org-article:4362270682cc4067a9e0e1c85c8766702021-11-18T06:06:20ZHeterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.1553-73661553-737410.1371/journal.ppat.1003040https://doaj.org/article/4362270682cc4067a9e0e1c85c8766702012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23166501/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Heterotrimeric 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 Gα subunit EhGα1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGβγ dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGα1 highlights unique features and classification outside of conventional mammalian Gα subfamilies. E. histolytica trophozoites overexpressing wildtype EhGα1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGα1-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 EhGα1 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.Dustin E BoschAdam J KimpleRobin E MullerPatrick M GiguèreMischa MachiusFrancis S WillardBrenda R S TempleDavid P SiderovskiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 11, p e1003040 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Dustin E Bosch Adam J Kimple Robin E Muller Patrick M Giguère Mischa Machius Francis S Willard Brenda R S Temple David P Siderovski Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
description	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 Gα subunit EhGα1 exhibits conventional nucleotide cycling properties and is seen to interact with EhGβγ dimers and a candidate effector, EhRGS-RhoGEF, in typical, nucleotide-state-selective fashions. In contrast, a crystal structure of EhGα1 highlights unique features and classification outside of conventional mammalian Gα subfamilies. E. histolytica trophozoites overexpressing wildtype EhGα1 in an inducible manner exhibit an enhanced ability to kill host cells that may be wholly or partially due to enhanced host cell attachment. EhGα1-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 EhGα1 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.
format	article
author	Dustin E Bosch Adam J Kimple Robin E Muller Patrick M Giguère Mischa Machius Francis S Willard Brenda R S Temple David P Siderovski
author_facet	Dustin E Bosch Adam J Kimple Robin E Muller Patrick M Giguère Mischa Machius Francis S Willard Brenda R S Temple David P Siderovski
author_sort	Dustin E Bosch
title	Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
title_short	Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
title_full	Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
title_fullStr	Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
title_full_unstemmed	Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.
title_sort	heterotrimeric g-protein signaling is critical to pathogenic processes in entamoeba histolytica.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4362270682cc4067a9e0e1c85c876670
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Heterotrimeric G-protein signaling is critical to pathogenic processes in Entamoeba histolytica.

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