YlBMH1 encodes a 14-3-3 protein that promotes filamentous growth in the dimorphic yeast Yarrowia lipolytica a aThe GenBank accession numbers for the YlBMH1 and YlBMH2 sequences reported in this study are AY090661 and AY090662, respectively.

Abstract

Most pathogenic fungi have the ability to alternate between a unicellular yeast form and different filamentous forms (hyphae and pseudohyphae). This attribute is generally regarded as an important virulence factor and has also attracted attention because of its implications in the study of eukaryotic cell differentiation. To identify genes that are involved in the regulation of these events, chemical mutagenesis of the dimorphic yeast Yarrowia lipolytica was performed and morphological mutants that were unable to form hyphal cells were isolated. Screening of a Y. lipolytica genomic DNA library for genes able to complement this defect led to the isolation of YlBMH1, a gene encoding a 14-3-3 protein and whose transcription levels are increased during the yeast-tohypha transition. Remarkably, overexpression of YlBMH1 was able to enhance pseudohyphae formation in a strain lacking functional YlRAC1 but caused no visible effects in ∆mhy1 and ∆bem1 cells, thus suggesting that YlBMH1 is involved in the regulation of both hyphal and pseudohyphal growth in Y. lipolytica. The identification of YlBMH2, a gene encoding a second 14-3-3 protein (YlBmh2p) that contains a 19 aa insertion absent in all other members of the 14-3-3 family, is also reported. Differently from YlBMH1, the transcription levels of YlBMH2 do not show any apparent variation during the induction of hyphal growth, and its overexpression has no effects on cells lacking functional MHY1, YlRAC1 or YlBEM1. Taken together, these observations suggest that, in spite of their high conservation, YlBmh1p and YlBmh2p have different cellular functions.

Ustilago maydis Rho1 and 14-3-3 Homologues Participate in Pathways Controlling Cell Separation and Cell Polarity

“…14-3-3 proteins have also been implicated in controlling filamentation in other dimorphic fungi, especially in C. albicans (37) and Y. lipolytica (16). In these organisms, the extent of filamentous growth is proportional to the level of 14-3-3 protein expression (16). More importantly, 14-3-3 proteins have also been shown to be essential for viability in S. cerevisiae (38), C. albicans (9), and S. pombe (19).…”

“…For example, in S. cerevisiae, 14-3-3 homologues Bmh1/Bmh2 regulate pseudohypha formation through the MAPK pathway (38). 14-3-3 proteins have also been implicated in controlling filamentation in other dimorphic fungi, especially in C. albicans (37) and Y. lipolytica (16). In these organisms, the extent of filamentous growth is proportional to the level of 14-3-3 protein expression (16).…”

“…14-3-3 functions have been associated with filamentous or pseudohyphal growth in C. albicans (37) and Yarrowia lipolytica. In C. albicans (30) and Y. lipolytica (16), strains with mutations in 14-3-3 proteins either develop abnormal filaments or fail to differentiate completely. To determine whether Pdc1 has any effect on aerial hyphae formation, we used pdc1 nar1 in otherwise wildtype-compatible mating types.…”

Decreased expression of 14-3-3 inParacoccidioides brasiliensisconfirms its involvement in fungal pathogenesis

“…In these microorganisms, the filamentous growth is proportional to the level of expression of the 14-3-3 protein. 38 Studies have shown that the variability of cell size within a fungal cell population alters pathogenicity via altering phagocytosis. 43,44 Phagocytosis, along with the resultant killing by macrophages and monocytes in the lungs, is one of the first lines of defense by the host immune system, 45 thus demonstrating that in P. brasiliensis, a decrease in cell size leads to increased phagocytosis and decreased virulence 44 .…”

“…37 Morphological transitions in dimorphic fungi are highly complex events triggered by a wide range of environmental factors and consisting of a reversible change in the growth pattern, alternating between the unicellular yeast form and the filamentous form (hyphae and pseudohyphae). 38 Understanding the mechanisms that regulate these events is of extreme interest due to implications for pathogenesis and cell differentiation, as observed with the inhibition of the transition to the parasitic form by the female hormone estrogen. 39 The proteins Bmph1p and Bmph2p in Saccharomyces cerevisiae are homologous to Pb14-3-3 and regulate pseudohyphal growth through the MAPK (mitogen-activated protein kinase) signaling pathway.…”