Analyses of G-protein mediated signals on the organization of the actin cytoskeleton, polar cell growth and the pathogenicity of Candida albicans

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GTP-binding proteins of Rho-family are central regulators of actin-cytoskeletal organization and thus determine cell shape and growth polarity of eukaryotic cells. G-protein signaling is essential for the dimorphic switch i.e. the change from yeastlike growth to hyphal growth of the human fungal pathogen Candida albicans which is required for its virulence. We could show that the Cawal 1 gene which encodes a Wiskott-Aldrich Syndrome-like protein is of key importance for the development of hyphae and the pathogenicity of C.albicans. Cawal1 mutants, however, are still able to bud and form pseudohyphae under inducing conditions. This ability suggests the presence of complex interacting signaling pathways which will be analyzed using dominant negative or constitutively active G-proteins and functional analyses of other potential mediators of Rho-signaling, particularly of formin-homologs or suppressors of the Cawal1 phenotype. Via in vivo time lapse and high-resolution fluorescence microscopy (using GFP-tagged proteins) subcellular protein localization of these proteins in C.albicans cells/hyphae over time is recorded to determine how processes of cell polarity establishment and polarized hyphal growth are linked and coordinated with each other in C.albicans.