Analyses of the role of RHO3 and of the WASP-homologue WAL1 for the maintenance of polarized hyphal growth in Candida albicans

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GTP-binding proteins of the Rho-family determine the organization of the actin cytoskeleton and thus morphogenesis and cell shape of eukaryotic cells. Polarized hyphal growth is regarded as a virulence factor of the human fungal pathogen Candida albicans. We could show that the C. albicans homologue of Wiskott-Aldrich Syndrome Proteins (WASP) is required for this process. The mechanism of CaWal1p activation is at present not understood particularly because fungal WASPs lack a G-protein binding domain in contrast to human WASP. Our previous work supports a connection between RHO3 and WAL1 for the organization of the actin cytoskeleton and the maintenance of polarized hyphal growth. In the proposed project a detailed characterization of CaRHO3 is carried out. Deletion mutants will be characterized and the transcriptional regulation of RHO3 during the dimorphic switch will be investigated. Via in vivo time lapse fluorescence microscopy spatial and temporal distribution of Rho3-GFP is determined. Two-hybrid analyses are applied to find additional components of a network that includes Rho3p and Wal1p. This allows to establish a mechanistic connection beween these two proteins and provides insights into the regulation of the cortical actin cytoskeleton and polarized hyphal growth in C. albicans.