Figure 6.

Cross-talk of GPI-GnT with Cyr1-cAMP-PKA pathway in Saccharomyces cerevisiae and Candida albicans. Shown in the figure are probable models of the cross-talk in (A) S. cerevisiae and (B) C. albicans. Ras proteins interact with the GPI-GnT at the ER during their transit to the PM. How this transition occurs is shown in Figure 5. This requires active Ras and, at least in S. cerevisiae, the effector loop. The interaction leads to inhibition of the GPI-GnT in S. cerevisiae and its activation in C. albicans. In C. albicans, only the Gpi2 subunit physically interacts with Ras. Perhaps the same subunit interacts with Ras in S. cerevisiae, but no clear-cut evidence exists for this. The GPI-GnT in S. cerevisiae inhibits the Cyr1-cAMP-PKA signaling. One possible model would be to assume that when bound to the GPI-GnT in the ER, the molecules of Ras available at the PM to activate cAMP production drop. This leads to the inhibition of filamentation. Downregulation of any of the GPI-GnT subunits releases Ras and activates filamentation. In C. albicans, overexpression of Gpi2 inhibits Hsp90, whose downregulation enables better interaction of Ras with Cyr1 and activates filamentation. If such an effect were to operate in S. cerevisiae, it would lead to inhibition of filamentation, since Hsc82 promotes the interaction of Ras with Cyr1 in this organism. But evidence in support of such a model is lacking. Filamentation in C. albicans is also activated by the direct binding of CO₂ to the cyclase domain of Cyr1, independent of Ras. The Eri1 subunit of the GPI-GnT inhibits this process. Double headed arrows represent protein–protein interactions, red flatheaded arrows represent inhibition, and blue arrows represents activation.