SUMMARY PARAGRAPH for HNM1
HNM1 encodes a high affinity permease involved in the active transport of choline and ethanolamine, which are used as precursors for the biosynthesis of phosphatidylcholine and phosphatidylethanolamine, respectively (9, 5, 4). During hypersaline stress, Hnm1p is involved in the uptake of glycine betaine as well as choline. When cells are exposed to high-salt stress, phosphatidylcholine turnover increases and choline is used for the biosynthesis of two methylamine osmoprotectants, glycerophosphocholine and glycine betaine (6). In HNM1 deletion mutants grown on high salt-containing medium, the transport of choline and glycine betaine is almost eliminated, as is the choline- and glycine betaine-mediated growth enhancement observed in wild-type cultures (6). Based on both functional and phylogenetic criteria, Hnm1p has been classified as a member of the amino acid/choline transporter (ACT) subfamily, TC 2.A.3.4, (10, 11), and by sequence similarity is most closely related to Uga4p, the yeast gamma-aminobutyrate (GABA) transporter (12).
In addition to its role in the transport of phospholipid biosynthetic precursors and osmoprotectants, HNM1 has been identified as a target of the toxic effects of the DNA alkylating agents nitrogen mustard (HN2) and nitrogen half-mustard, such that these compounds competitively inhibit choline transport (8, 13). Mutant strains defective in choline transport are nitrogen mustard hyper-resistant, while HNM1 overexpression results in HN2 hyper-sensitivity that is dependent upon the concentration of choline and inositol in the growth medium, and the cellular capacity to repair HN2-induced DNA damage (8, 1, 13).
Expression of HNM1 is co-regulated along with genes involved in phospholipid biosynthesis (3). HNM1 transcription is strongly repressed by the phospholipid precursors myo-inositol and choline, with myo-inositol alone having a weak repressive effect (4, 3). Two promoter regions contribute to this regulation, a UAS-INO element that is responsive to transcriptional activators, Ino2p and Ino4p, as well as the transcriptional corepressor, Opi1p and a second region that responds to Ino4p, but not Ino2p (3).
Last updated: 2008-02-28