Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease

The SSY1 gene of Saccharomyces cerevisiae encodes a member of a large famil y of amino acid permeases. Compared to the 17 other proteins of this family , however, Ssy1p displays unusual structural features reminiscent of those distinguishing the Snf3p and Rgt2p glucose sensors from the other proteins of the sugar transporter family. We show here that SSY1 is required for tra nscriptional induction, in response to multiple amino acids, of the AGP1 ge ne encoding a low-affinity, broad-specificity amino acid permease. Total no ninduction of the AGP1 gene in the ssy1 Delta mutant is not due to impaired incorporation of inducing amino acids. Conversely, AGP1 is strongly induce d by tryptophan in a mutant strain largely deficient in tryptophan uptake, but it remains unexpressed in a mutant that accumulates high levels of tryp tophan endogenously. Induction of AGP1 requires Uga35p(Dal81p/DurLp), a tra nscription factor of the Cys(6)-Zn-2 family previously shown to participate in several nitrogen induction pathways. Induction of AGP1 by amino acids a lso requires Grr1p, the F-box protein of the SCFGrr1 ubiquitin-protein liga se complex also required for transduction of the glucose signal generated b y the Snf3p and Rgt2p glucose sensors. Systematic analysis of amino acid pe rmease genes showed that Ssy1p is involved in transcriptional induction of at least five genes in addition to AGP1. Our results show that the amino ac id permease homologue Ssy1p is a sensor of external amino acids, coupling a vailability of amino acids to transcriptional events. The essential role of Grr1p in this amino acid signaling pathway lends further support to the hy pothesis that this protein participates in integrating nutrient availabilit y with the cell cycle.