High impact information on SNF3

• Recent studies of Saccharomyces cerevisiae revealed sensors that detect extracellular amino acids (Ssy1p) or glucose (Snf3p and Rgt2p) and are evolutionarily related to the transporters of these nutrients [1].
• This same mutation introduced into SNF3 also causes glucose-independent expression of HXT genes [2].
• We have identified another apparent glucose transporter, Rgt2p, that is strikingly similar to Snf3p and is required for maximal induction of gene expression in response to high levels of glucose [2].
• The predicted amino acid sequence shows that SNF3 encodes a 97-kilodalton protein that is homologous to mammalian glucose transporters and has 12 putative membrane-spanning regions [3].
• We report here the nucleotide sequence of the cloned SNF3 gene [3].

Biological context of SNF3

• DDSE: downstream targets of the SNF3 signal transduction pathway [4].
• An additional mechanism for glucose sensing must exist since a strain lacking all four genes (snf3 rgt2 std1 mth1) is still able to regulate SUC2 gene expression in response to changes in glucose concentration [5].
• The function of another new member of the HXT superfamily, HXT4 (previously identified by its ability to suppress the snf3 delta phenotype; L. Bisson, personal communication), was revealed in experiments that deleted all possible combinations of the five members of the glucose transporter gene family [6].
• DNA sequence dependent suppressing elements (DDSEs) are regions located in the promoters of yeast glucose transporter (HXT) genes that when present in high copy suppress the snf3 growth defect [4].
• Expression was elevated to a high level in an rgt1 mutant in the absence of Snf3p suggesting that this DDSE region contains binding sites for the Rgt1p transcriptional repressor/activator [4].

Anatomical context of SNF3

• In snf3 delta cells expression of HXT6 is constitutive even when the entire repertoire of HXT genes is present and glucose uptake is abundant [7].
• In this work, we show that glucose-induced activation of plasma membrane H(+)-ATPase from Saccharomyces cerevisiae is strongly dependent on calcium metabolism and that the glucose sensor Snf3p works in a parallel way with the G protein Gpa2p in the control of the pathway [8].
• We also show that Snf3p could be involved in the control of Pmc1p activity that would regulate the calcium availability in the cytosol [8].

Associations of SNF3 with chemical compounds

• Disruption of the HXT1 gene resulted in loss of a portion of high-affinity glucose and mannose transport, and wild-type levels of transport required both the HXT1 and SNF3 genes [9].
• Loss of the SNF3 gene leads to a long-term adaptation phenotype for cells grown in liquid medium at low substrate concentrations in the presence of the respiratory inhibitor, antimycin A [10].
• In addition, the growth properties of snf3 mutants suggested that they were defective in uptake of glucose and fructose [11].
• High basal activity of the HXT7 promoter during growth on ethanol required Snf3 as well as other components of the signalling pathway activated by Snf3 [12].

Physical interactions of SNF3

• A two-hybrid screen revealed that the Mth1 protein interacts with the cytoplasmic tails of the glucose sensors Snf3 and Rgt2 [13].
• Multicopy HXT4 increases both high and low affinity glucose transport in snf3 strains and increases low and high transport in wild-type strains [14].
• Multicopy expression of the HXT1 gene restored high-affinity glucose transport to the snf3 mutant, which is deficient in a significant proportion of high-affinity glucose transport [9].
• The HXT2 gene of the yeast Saccharomyces cerevisiae was identified on the basis of its ability to complement the defect in glucose transport of a snf3 mutant when present on the multicopy plasmid pSC2 [15].
• Kinetic analysis of glucose uptake showed that the rgt1 and RGT2 suppressors restore glucose-repressible high-affinity glucose transport in a snf3 mutant [16].

Enzymatic interactions of SNF3

• We present evidences indicating that Snf3p would be the sensor for the internal signal (phosphorylated sugars) of this pathway that would connect calcium signaling and activation of the plasma membrane ATPase [8].
• Only in the strain with genes HXT1-4 and SNF3 deleted but carrying HXT6/7 were glucose uptake kinetics and invertase activity independent of the presence or concentration of glucose in the growth medium [17].

Regulatory relationships of SNF3

• Mutations in MTH1 can suppress the raffinose growth defect of a snf3 mutant as well as the glucose fermentation defect present in cells lacking both glucose sensors (snf3 rgt2) [5].
• A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6 [7].
• Similarly, Hxt2p was found to be expressed under low-glucose conditions in an snf3 mutant which does not display high-affinity uptake [18].

Other interactions of SNF3

• Rgt2p, which along with Snf3p monitors extracellular glucose levels, appears to be the glucose sensor for the glucose-transport-independent pathway [19].
• Nevertheless the expression of glucose-repressible HXT3 and SNF3 genes is significantly reduced [20].
• This finding suggests that SNF3 may be involved in the posttranslational regulation of Hxt2p [18].
• These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways [21].
• The GAL2 protein is related to the yeast glucose transporter encoded by the SNF3 gene, and also to mammalian and bacterial sugar permeases [22].

References