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Fungal Genet Biol. 2013 Aug;57:58-75. doi: 10.1016/j.fgb.2013.05.006. Epub 2013 Jun 5.

Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans.

Author information

1
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.

Abstract

A genome wide analysis of the human fungal pathogen Cryptococcus neoformans var. grubii has revealed a number of duplications of highly conserved genes involved in morphogenesis. Previously, we reported that duplicate Cdc42 paralogs provide C. neoformans with niche-specific responses to environmental stresses: Cdc42 is required for thermotolerance, while Cdc420 supports the formation of titan cells. The related Rho-GTPase Rac1 has been shown in C. neoformans var. neoformans to play a major role in filamentation and to share Cdc42/Cdc420 binding partners. Here we report the characterization of a second Rac paralog in C. neoformans, Rac2, and describe its overlapping function with the previously described CnRac, Rac1. Further, we demonstrate that the Rac paralogs play a primary role in polarized growth via the organization of reactive oxygen species and play only a minor role in the organization of actin. Finally, we provide preliminary evidence that pharmacological inhibitors of Rac activity and actin stability have synergistic activity.

KEYWORDS:

Cryptococcus neoformans; Hyphal growth; Paralogs; Polarization; ROS; Rac GTPase

PMID:
23748012
PMCID:
PMC3742549
DOI:
10.1016/j.fgb.2013.05.006
[Indexed for MEDLINE]
Free PMC Article

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