Article

Two CDC42 paralogues modulate Cryptococcus neoformans thermotolerance and morphogenesis under host physiological conditions.

Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
Molecular Microbiology (impact factor: 5.01). 12/2009; 75(3):763-80. DOI:10.1111/j.1365-2958.2009.07019.x pp.763-80
Source: PubMed

ABSTRACT The precise regulation of morphogenesis is a key mechanism by which cells respond to a variety of stresses, including those encountered by microbial pathogens in the host. The polarity protein Cdc42 regulates cellular morphogenesis throughout eukaryotes, and we explore the role of Cdc42 proteins in the host survival of the human fungal pathogen Cryptococcus neoformans. Uniquely, C. neoformans has two functional Cdc42 paralogues, Cdc42 and Cdc420. Here we investigate the contribution of each paralogue to resistance to host stress. In contrast to non-pathogenic model organisms, C. neoformans Cdc42 proteins are not required for viability under non-stress conditions but are required for resistance to high temperature. The paralogues play differential roles in actin and septin organization and act downstream of C. neoformans Ras1 to regulate its morphogenesis sub-pathway, but not its effects on mating. Cdc42, and not Cdc420, is upregulated in response to temperature stress and is required for virulence in a murine model of cryptococcosis. The C. neoformans Cdc42 proteins likely perform complementary functions with other Rho-like GTPases to control cell polarity, septin organization and hyphal transitions that allow survival in the environment and in the host.

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Keywords

act downstream
 
C. neoformans
 
C. neoformans Cdc42 proteins
 
C. neoformans Cdc42 proteins likely
 
C. neoformans Ras1
 
Cdc42 proteins
 
complementary functions
 
control cell polarity
 
host stress
 
human fungal pathogen Cryptococcus neoformans
 
hyphal transitions
 
key mechanism
 
microbial pathogens
 
morphogenesis sub-pathway
 
non-pathogenic model organisms
 
non-stress conditions
 
polarity protein Cdc42 regulates cellular morphogenesis
 
precise regulation
 
Rho-like GTPases
 
temperature stress