Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.

Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, and Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies of all three, provides a unique model in which to examine the...

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Autores principales:	Elizabeth Ripley Ballou, Lukasz Kozubowski, Connie B Nichols, J Andrew Alspaugh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/7362b4eb538749339cfb83ae02399eef
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spelling	oai:doaj.org-article:7362b4eb538749339cfb83ae02399eef2021-11-18T06:22:03ZRas1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.1553-73901553-740410.1371/journal.pgen.1003687https://doaj.org/article/7362b4eb538749339cfb83ae02399eef2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23950731/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, and Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies of all three, provides a unique model in which to examine the interactions of these conserved proteins. Previously, we demonstrated that RAS1 mediates C. neoformans virulence by acting as a central regulator of both thermotolerance and mating. We report here that ras1Δ mutants accumulate defects in polarized growth, cytokinesis, and cell cycle progression. We demonstrate that the ras1Δ defects in thermotolerance and mating can be largely explained by the compromised activity of four downstream Rho-GTPases: the Cdc42 paralogs, Cdc42 and Cdc420; and the Rac paralogs, Rac1 and Rac2. Further, we demonstrate that the separate GTPase classes play distinct Ras-dependent roles in C. neoformans morphogenesis and pathogenesis. Cdc42 paralogs primarily control septin localization and cytokinesis, while Rac paralogs play a primary role in polarized cell growth. Together, these duplicate, related signaling proteins provide a robust system to allow microbial proliferation in the presence of host-derived cell stresses.Elizabeth Ripley BallouLukasz KozubowskiConnie B NicholsJ Andrew AlspaughPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 9, Iss 8, p e1003687 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Elizabeth Ripley Ballou Lukasz Kozubowski Connie B Nichols J Andrew Alspaugh Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
description	Proliferation and morphogenesis in eukaryotic cells depend on the concerted activity of Rho-type GTPases, including Ras, Cdc42, and Rac. The sexually dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential copies of all three, provides a unique model in which to examine the interactions of these conserved proteins. Previously, we demonstrated that RAS1 mediates C. neoformans virulence by acting as a central regulator of both thermotolerance and mating. We report here that ras1Δ mutants accumulate defects in polarized growth, cytokinesis, and cell cycle progression. We demonstrate that the ras1Δ defects in thermotolerance and mating can be largely explained by the compromised activity of four downstream Rho-GTPases: the Cdc42 paralogs, Cdc42 and Cdc420; and the Rac paralogs, Rac1 and Rac2. Further, we demonstrate that the separate GTPase classes play distinct Ras-dependent roles in C. neoformans morphogenesis and pathogenesis. Cdc42 paralogs primarily control septin localization and cytokinesis, while Rac paralogs play a primary role in polarized cell growth. Together, these duplicate, related signaling proteins provide a robust system to allow microbial proliferation in the presence of host-derived cell stresses.
format	article
author	Elizabeth Ripley Ballou Lukasz Kozubowski Connie B Nichols J Andrew Alspaugh
author_facet	Elizabeth Ripley Ballou Lukasz Kozubowski Connie B Nichols J Andrew Alspaugh
author_sort	Elizabeth Ripley Ballou
title	Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
title_short	Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
title_full	Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
title_fullStr	Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
title_full_unstemmed	Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
title_sort	ras1 acts through duplicated cdc42 and rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen cryptococcus neoformans.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7362b4eb538749339cfb83ae02399eef
work_keys_str_mv	AT elizabethripleyballou ras1actsthroughduplicatedcdc42andracproteinstoregulatemorphogenesisandpathogenesisinthehumanfungalpathogencryptococcusneoformans AT lukaszkozubowski ras1actsthroughduplicatedcdc42andracproteinstoregulatemorphogenesisandpathogenesisinthehumanfungalpathogencryptococcusneoformans AT conniebnichols ras1actsthroughduplicatedcdc42andracproteinstoregulatemorphogenesisandpathogenesisinthehumanfungalpathogencryptococcusneoformans AT jandrewalspaugh ras1actsthroughduplicatedcdc42andracproteinstoregulatemorphogenesisandpathogenesisinthehumanfungalpathogencryptococcusneoformans
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Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.

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