Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

Abstract

In Candida albicans, Myo5p and Sla2p are required for the polarized localization and function of cortical actin patches, for hyphal formation, and for endocytosis. Deletion of either the MYO5 or the SLA2 gene generated a common transcriptional response that involved changes in the transcript levels of cell wall proteinand membrane protein-encoding genes. However, these profiles were distinct from those observed for a mutant with specific deletions of the actin-organizing domains of Myo5p or for wild-type cells treated with cytochalasin A, both of which also generate defects in the organization of cortical actin patches. The profiles observed for the myo5⌬ and sla2⌬ mutants had similarities to those of wild-type cells subjected to an osmotic shock, and the defects in cortical patch function found with myo5⌬ and sla2⌬ mutants, but not cortical actin patch distribution per se, affected sensitivity to various stresses, including heat and osmotic shocks and cell wall damage. Secondary effects coupled with defective endocytosis, such as lack of polarized lipid rafts and associated protein Rvs167-GFP (where GFP is green fluorescent protein) and lack of polarized wall remodeling protein GFP-Gsc1, were also observed for the myo5⌬ and sla2⌬ mutants. The mitogen-activated protein kinases Hog1p and Mkc1p, which mediate signaling in response to osmotic stress and cell wall damage, do not play a major role in regulating the transcript level changes in the myo5⌬ and sla2⌬ mutants. Hog1p was not hyperphosphorylated in the myo5⌬ and sla2⌬ mutants, and the transcript levels of only a subset of genes affected in the myo5⌬ mutant were dependent upon the presence of Hog1p and Mkc1p. However, it appears that Hog1p and Mkc1p play important roles in the myo5⌬ mutant cells because double deletion of myosin I and either Hog1p or Mkc1p resulted in very-slow-growing cells.

BAR Domain Proteins Rvs161 and Rvs167 Contribute to Candida albicans Endocytosis, Morphogenesis, and Virulence

“…Endocytosis and morphogenesis are interrelated; efficient endocytosis is thought to be critical for the appropriate localization of proteins required for polarized morphogenesis (35). Consistent with this, rvs161⌬ was more defective than rvs167⌬ in both endocytosis and hyphal morphogenesis, and a similar correlation was reported for mutations in other C. albicans genes, including WAL1, SLA2, and MYO5 (29,30,43). Interestingly, the rvs161⌬ and rvs167⌬ mutants formed extensive filamentous growth in the kidney, suggesting that stronger inducing signals in vivo improved filamentous growth (Fig.…”

“…It was suggested previously that endocytosis may also play a role in forming a special lipid domain at the hyphal tips (25,30), which is thought to contribute to highly polarized hyphal morphogenesis and may influence the response to antifungal drugs (2). Surprisingly, the rvs⌬ strains still exhibited enriched filipin staining of sterols at the hyphal tips (Fig.…”

“…to their more severe defect in actin organization (30). Actin filaments are important for polarized filipin staining (25).…”

Sterol-Rich Plasma Membrane Domains in Fungi

“…However, there are potential similarities, since C. albicans mutants with defects in myosin I (Myo5) or the actin-related protein Sla2 did not display SRDs, although these results are complicated by the fact that the mutants are also defective in forming hyphae (64). There are also similarities in the mechanisms of SRD formation in S. pombe and A. nidulans, in which the MesA protein is needed both to form SRDs at hyphal tips and for proper localization of the formin SepA (67).…”

The Candida albicans phosphatase Inp51p interacts with the EH domain protein Irs4p, regulates phosphatidylinositol-4,5-bisphosphate levels and influences hyphal formation, the cell integrity pathway and virulence

“…The disease-causing capacity of mutant C. albicans strains that are unable to switch between yeast and hyphal morphologies is generally attenuated (Calderone & Fonzi, 2001;Kumamoto & Vinces, 2005). The identification of proteins and protein complexes that might be responsible for coordinating the multiple cellular processes that contribute to efficient morphogenesis has become an active area of research (Brand et al, 2007;Hausauer et al, 2005;Li et al, 2005;Martin & Konopka, 2004;Oberholzer et al, 2006;Walther & Wendland, 2004;Zheng et al, 2003).…”