ZDS1 AND ZDS2, GENES WHOSE PRODUCTS MAY REGULATE CDC42P IN SACCHAROMYCES-CEREVISIAE

A genetic screen for GTPase-activating proteins (GAPs) or other negati ve regulators of the Rac/Rho family GTPase Cdc42p in Saccharomyces cer evisiae identified ZDS1, a gene encoding a protein of 915 amino acids. Sequence from the yeast genome project identified a homolog, ZDS2, wh ose predicted product of 942 amino acids is 38% identical in sequence to Zds1p. Zds1p and Zds2p have no detectable homology to known Rho-GAP s or to other known proteins. However, by several assays, it appears t hat overexpression of either Zds1p or Zds2p decreases the level of Cdc 42p activity. Deletion analysis also suggests that Zds1p and Zds2p are at least partially overlapping in function, Deletion of ZDS2 produced no obvious phenotype, and deletion of ZDS1 produced no obvious phenot ype other than a mild effect on cell shape. However, the zds1 zds2 dou ble mutant grew slowly with an apparent mitotic delay and produced elo ngated cells and buds with other evidence of abnormal morphogenesis. A glutathione S-transferase-Zds1p fusion protein that fully complemente d the double mutant localized to presumptive bud sites and the tips of small buds, The similarity of this localization to that of Cdc42p sug gests that Zds1p may interact directly with Cdc42p.As ZDS1 and ZDS2 ha ve recently been identified also by numerous other groups studying a w ide range of biological phenomena, the roles of Cdc42p in intracellula r signaling mag be more diverse than has previously been appreciated.