Ras signaling is required for serum-induced hyphal differentiation in Candida albicans

Serum induces Candida albicans to make a rapid morphological change from th e yeast cell form to hyphae, Contrary to the previous reports, we found tha t serum albumin does not play a critical role in this morphological change. Instead, a filtrate (molecular mass, <1 kDa) devoid of serum albumin induc es hyphae, To study genes controlling this response, we have isolated the R AS1 gene from C. albicans by complementation. The Candida Ras1 protein, lik e Ras1 and Ras2 of Saccharomyces cerevisiae, has a long C-terminal extensio n. Although RAS1 appears to be the only RAS gene present in the C. albicans genome, strains homozygous for a deletion of RAS1 (ras1-2/ras1-3) are viab le. The Candida ras1-2/ras1-3 mutant fails to form germ tubes and hyphae in response to serum or to a serum filtrate but does form pseudohyphae. Moreo ver, strains expressing the dominant active RAS1(V13) allele manifest enhan ced hyphal growth, whereas those expressing a dominant negative RAS1(A16) a llele show reduced hyphal growth. These data show that low-molecular-weight molecules in serum induce hyphal differentiation in C. albicans through a Ras-mediated signal transduction pathway.