Expression of a constitutively active Cdc42 homologue promotes developmentof sclerotic bodies but represses hyphal growth in the zoopathogenic fungus Wangiella (Exophiala) dermatitidis

In contrast to the CDC42 homologues of Saccharomyces cerevisiae and Schizos accharomyces pombe, the WdCDC42 gene in the human pathogenic fungus Wangiel la (Exophiala) dermatitidis was found to be nonessential for cell viability . Expression of the constitutively active allele wdcdc42(G14V) at 37 degree s C induced nonpolarized growth that led to cell enlargement and multiple n ucleation. The swollen cells subsequently converted into planate divided bi cellular forms or multiply septated sclerotic bodies in post-log phase, whe n the G14V-altered protein was diminished. The wdcdc42(G14V) mutation also strongly repressed filamentous growth both in the wild-type strain and in t he temperature-sensitive hyphal-form mutant Hf1. In contrast, overexpressio n of the dominant negative alleles wdcdc42(T19N) and wdcdc42(D120A) had no obvious effect on fungal-cell polarization. These results suggested that Wd Cdc42p plays a unique regulatory role in cellular morphogenesis in W. derma titidis. Activation of this protein in response to extracellular or intrace llular signals seems to commit its yeast-like cells to a phenotype transiti on that produces sclerotic bodies while repressing hyphal development.