The Gpr1/Fun34/YaaH Protein Family in the Nonconventional Yeast Yarrowia lipolytica and the Conventional Yeast Saccharomyces cerevisiae

Abstract

The sequencing of the genomes of several organisms was the first step in understanding genome organisation, gene function and of course life itself. Until now very much information could be gained by searching for similarities between genes or structures and finding homologies or direct orthologous genes. But with the sequencing data, more and more questions arise, which cannot be answered by simply looking the data. Although the yeast Saccharomyces cerevisiae was the first eukaryotic organism, the genome of which was sequenced, almost 14 years later there are still 900 uncharacterised and 800 dubious genes (26 % at all). The unconventional yeast Yarrowia lipolytica also harbours a high number of genes with unknown function-ca. 2,300 (35 %). One hundred seventy out of 220 Yarrowia lipolytica specific genes with no homology to other yeasts are also uncharacterised, which should carry the "differences" between the yeast species. So far only 50 industrial useful genes were characterised (proteases, lipases, esterases, etc.).Genes or gene products that do not have any known function have to be analysed in a more classical, genetical way. Especially the functions of membrane proteins which are resistant to a lot of investigation steps are only rarely elucidated. The Gpr1 protein of Yarrowia lipolytica is such an example. The function cannot be estimated by finding similarities to other proteins with known function. The more the information and phenotypic effects are available, the more complex the interacting network appears. This chapter will show the ongoing discovery of the function of the Gpr1/FUN34/YaaH protein family. This is especially shown for the Gpr1 protein from Yarrowia lipolytica and its orthologues in Saccharomyces cerevisiae. Here the different and also controversial facts are reviewed and discussed.

The acetate uptake transporter family motif “NPAPLGL(M/S)” is essential for substrate uptake

“…Gpr1p was reported to have an important role over stress cue, triggered by the exposure of cells to acetic acid, and to be involved in the repression of genes that encode glyoxylate cycle enzymes (Augstein et al, 2003;Tzschoppe et al, 1999). Fluorescence microscopy analysis of S. cerevisiae cells harbouring Gpr1-GFP revealed that the fusion protein was detected at the plasma membrane, as previously reported (Augstein et al, 2003;Matthäus and Barth, 2013). The yeast Y. lipolytica displays specific physiological, metabolic and genomic characteristics, which differentiates it from the model yeast S. cerevisiae (Nicaud, 2012).…”

The lichen symbiosis re-viewed through the genomes of Cladonia grayi and its algal partner Asterochloris glomerata

“…Of the four MEthylammonium Permease-type (MEP) ammonium transporters in the C. grayi mycobiont, two belong to the general fungal class (CLAGR_000407-RA and CLAGR_009781-RA) and two to the class primarily retained by lichens (CLAGR_005848-RA and CLAGR_003366-RA). The Cladonia mycobiont also has four transporters belonging to the Gpr1/FUN34/YaaH family, whose functions are debated [130] but include the postulated ability to export NH 4 + in yeast [128], where they are named ATO (Ammonia Transport Outward). The differential transcription of these eight transporter genes is interesting: relative to fungal monoculture, in coculture with the alga five are repressed, two are induced (one strongly), and one is unchanged (Table 3).…”

New insights into the acetate uptake transporter (AceTr) family: Unveiling amino acid residues critical for specificity and activity

“…Furthermore, single amino acid substitutions A70V, F71V, T74I, A88V, E144G, N145D, M211K, and F212S within Ato1 and N75D, G147D, and S265L within Ato2 were discovered to produce the same hypersensitive effect in S. cerevisiae [24] , showing that induction of acetic acid sensitivity is not exclusive for GPR1 mutants. While specific single amino acid substitutions in Gpr1, Ato1 and Ato2 were able to cause such drastic inhibitory effects, surprisingly, knockout of GPR1 in Y. lipolytica or triple knockout of ATO1 , ATO2 and ATO3 in S. cerevisiae did not cause any phenotypic changes [25] .…”