GPI2 encodes for one of the six accessory subunits of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the first step of GPI biosynthesis in S. cerevisiae and C. albicans. It has been previously reported in S. cerevisiae that this subunit physically interacts with and negatively modulates Ras signaling. On the other hand, studies from our lab have shown that the homologous subunit in C. albicans is a positive modulator of Ras signaling. Are the functions of this subunit therefore strictly species dependent? We present here functional complementation studies on GPI2 from S. cerevisiae and C. albicans that were carried out to address this issue. Expression of CaGPI2 in a ScGPI2 conditional lethal mutant could not restore its growth defects. Likewise, ScGPI2 overexpression in a CaGPI2 heterozygous mutant could not restore its deficient GPI-GnT activity or reverse defects in its cell wall integrity and could only poorly restore filamentation. However, interestingly, ScGPI2 could restore lanosterol demethylase (CaERG11) levels and reverse azole resistance of the CaGPI2 heterozygote. It appeared to do this by regulating levels of another GPI-GnT subunit, CaGPI19, which we have previously shown to be involved in cross-talk with CaERG11. Thus, the effect of CaGPI2 on sterol biosynthesis in C. albicans is independent of its interaction with the GPI-GnT complex and Ras signaling pathways. In addition, the interaction of Gpi2 with other subunits of the GPI-GnT complex as well as with Ras signaling appears to have evolved differently in the two organisms.

• PMID: 25117514
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Yadav A, Singh SL, Yadav B, Komath SS

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