Roles of the three Ras proteins in the regulation of dimorphic transition in the yeastYarrowia lipolytica

Ras proteins in the budding yeast Saccharomyces cerevisiae are essential for growth and dimorphic transition. The dimorphic yeast Yarrowia lipolytica is distantly related to S. cerevisiae. Its genome encodes three Ras proteins. Here, we show that the three Ras proteins in Y. lipolytica are critical for dimorphic transition but are dispensable for growth. Among the three Ras proteins, YlRas2 plays a major role in the regulation of dimorphic transition, whereas YlRas1 plays a minor role in this process. The additional Ras protein, YlRas3, which resembles mammalian K-Ras4B at the C-terminus, does not seem to have a significant role in dimorphic transition. Thus, the three Ras proteins do not act equally in the regulation of dimorphic transition. We also show that the expression of YlRAS2 was increased dramatically at the transcriptional level during yeast-to-hypha transition, consistent with a major role of YlRas2 in the regulation of dimorphic transition. YlRas2's function in dimorphic transition depends on the active GTP-bound form of YlRas2 and its localization to the plasma membrane. YlRas2 could also partially function on the endomembranes. In addition, we identified the transcription factor Mhy1 as a potential signal transducer downstream of YlRas2 in the control of dimorphic transition. This finding suggests that novel signaling pathway controlled by Ras proteins regulating dimorphic transition may exist in Y. lipolytica.