Expression of a Constitutively Active Cdc42 Homologue Promotes Development of Sclerotic Bodies but Represses Hyphal Growth in the Zoopathogenic Fungus Wangiella ( Exophiala ) dermatitidis

Abstract

ABSTRACT In contrast to the CDC42 homologues of Saccharomyces cerevisiae and Schizosaccharomyces pombe , the WdCDC42 gene in the human pathogenic fungus Wangiella ( Exophiala ) dermatitidis was found to be nonessential for cell viability. Expression of the constitutively active allele wdcdc42 G14V at 37°C induced nonpolarized growth that led to cell enlargement and multiple nucleation. The swollen cells subsequently converted into planate divided bicellular forms or multiply septated sclerotic bodies in post-log phase, when the G14V-altered protein was diminished. The wdcdc42 G14V mutation also strongly repressed filamentous growth both in the wild-type strain and in the temperature-sensitive hyphal-form mutant Hf1. In contrast, overexpression of the dominant negative alleles wdcdc42 T19N and wdcdc42 D120A had no obvious effect on fungal-cell polarization. These results suggested that WdCdc42p plays a unique regulatory role in cellular morphogenesis in W. dermatitidis . Activation of this protein in response to extracellular or intracellular signals seems to commit its yeast-like cells to a phenotype transition that produces sclerotic bodies while repressing hyphal development.