Sul1 and Sul2 sulfate transceptors signal to protein kinase A upon exit of sulfur starvation.

Sulfate is an essential nutrient with pronounced regulatory effects on cellular metabolism and proliferation. Little is known, however, about how sulfate is sensed by cells. Sul1 and Sul2 are sulfate transporters in the yeast Saccharomyces cerevisiae, strongly induced upon sulfur starvation and endocytosed upon the addition of sulfate.

Specific analogues uncouple transport, signalling, oligo-ubiquitination and endocytosis in the yeast Gap1 amino acid transceptor.

The Saccharomyces cerevisiae amino acid transceptor Gap1 functions as receptor for signalling to the PKA pathway and concomitantly undergoes substrate-induced oligo-ubiquitination and endocytosis. We have identified specific amino acids and analogues that uncouple to certain extent signalling, transport, oligo-ubiquitination and endocytosis. L-lysine, L-histidine and L-tryptophan are transported by Gap1 but do not trigger signalling.

Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae has been a favorite organism for pioneering studies on nutrient-sensing and signaling mechanisms. Many specific nutrient responses have been elucidated in great detail. This has led to important new concepts and insight into nutrient-controlled cellular regulation.

Yeast nutrient transceptors provide novel insight in the functionality of membrane transporters.

In the yeast Saccharomyces cerevisiae several nutrient transporters have been identified that possess an additional function as nutrient receptor. These transporters are induced when yeast cells are starved for their substrate, which triggers entry into stationary phase and acquirement of a low protein kinase A (PKA) phenotype. Re-addition of the lacking nutrient triggers exit from stationary phase and sudden activation of the PKA pathway, the latter being mediated by the nutrient transceptors.

Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant.

Peptides induce persistent signaling from endosomes by a nutrient transceptor.

The yeast Gap1 transceptor mediates amino acid activation of the protein kinase A pathway and undergoes endocytic internalization following amino acid transport. We identified three specific γ-glutamyl dipeptides that cause persistent cyclic AMP-independent activation of protein kinase A, prevent Gap1 vacuolar sorting and cause Gap1 accumulation in endosomes. To our knowledge, these are the first examples of persistent agonists of a transceptor.

From transporter to transceptor: signaling from transporters provokes re-evaluation of complex trafficking and regulatory controls: endocytic internalization and intracellular trafficking of nutrient transceptors may, at least in part, be governed by their signaling function.

When cells are starved of their substrate, many nutrient transporters are induced. These undergo rapid endocytosis and redirection of their intracellular trafficking when their substrate becomes available again. The discovery that some of these transporters also act as receptors, or transceptors, suggests that at least part of the sophisticated controls governing the trafficking of these proteins has to do with their signaling function rather than with control of transport.

Saccharomyces cerevisiae plasma membrane nutrient sensors and their role in PKA signaling.

The ability to elicit a fast intracellular signal leading to an adaptive response is crucial for the survival of microorganisms in response to changing environmental conditions. Therefore, in order to sense changes in nutrient availability, the yeast Saccharomyces cerevisiae has evolved three different classes of nutrient-sensing proteins acting at the plasma membrane: G protein-coupled receptors or classical receptor proteins, which detect the presence of certain nutrients and activate signal transduction in association with a G protein; nontransporting transceptors, i.e.

Novel mechanisms in nutrient activation of the yeast protein kinase A pathway.

In yeast the Protein Kinase A (PKA) pathway can be activated by a variety of nutrients. Fermentable sugars, like glucose and sucrose, trigger a spike in the cAMP level, followed by activation of PKA and phosphorylation of target proteins causing a.o.

Urmylation controls Nil1p and Gln3p-dependent expression of nitrogen-catabolite repressed genes in Saccharomyces cerevisiae.

Urm1 is a modifier protein that is conjugated to substrate proteins through thioester formation with the E1-like enzyme, Uba4. Here is shown that the lack of urmylation causes derepression of the GAP1 gene (encoding a nitrogen-regulated broad-spectrum amino acid-scavenging permease) in the presence of rich nitrogen sources, and simultaneous inhibition of the expression of CIT2, a TCA-cycle gene involved in the production of glutamate and glutamine. This effect is dependent on the TORC1- and nutrient-regulated transcriptional factors, Nil1p and Gln3p.

Amino acids regulate retrieval of the yeast general amino acid permease from the vacuolar targeting pathway.

Intracellular sorting of the general amino acid permease (Gap1p) in Saccharomyces cerevisiae depends on availability of amino acids such that at low amino acid concentrations Gap1p is sorted to the plasma membrane, whereas at high concentrations Gap1p is sorted to the vacuole. In a genome-wide screen for mutations that affect Gap1p sorting we identified deletions in a subset of components of the ESCRT (endosomal sorting complex required for transport) complex, which is required for formation of the multivesicular endosome (MVE). Gap1p-GFP is delivered to the vacuolar interior by the MVE pathway in wild-type cells, but when formation of the MVE is blocked by mutation, Gap1p-GFP efficiently cycles from this compartment to the plasma membrane, resulting in unusually high permease activity at the cell surface.

Endless versatility in the biotechnological applications of Kluyveromyces LAC genes.

Most microorganisms adapted to life in milk owe their ability to thrive in this habitat to the evolution of mechanisms for the use of the most abundant sugar present on it, lactose, as a carbon source. Because of their lactose-assimilating ability, Kluyveromyces yeasts have long been used in industrial processes involved in the elimination of this sugar. The identification of the genes conferring Kluyveromyces with a system for permeabilization and intracellular hydrolysis of lactose (LAC genes), along with the current possibilities for their transfer into alternative organisms through genetic engineering, has significantly broadened the industrial profitability of lactic yeasts.

A comparative analysis of the GAL genetic switch between not-so-distant cousins: Saccharomyces cerevisiae versus Kluyveromyces lactis.

Despite their close phylogenetic relationship, Kluyveromyces lactis and Saccharomyces cerevisiae have adapted their carbon utilization systems to different environments. Although they share identities in the arrangement, sequence and functionality of their GAL gene set, both yeasts have evolved important differences in the GAL genetic switch in accordance to their relative preference for the utilization of galactose as a carbon source. This review provides a comparative overview of the GAL-specific regulatory network in S.

Lactose: the milk sugar from a biotechnological perspective.

Lactose is a very important sugar because of its abundance in the milk of humans and domestic animals. Lactose is a valuable asset as a basic nutrient and the main substrate in fermentative processes that led to the production of fermented milk products, such as yogurt and kefir. In some instances, lactose also can be a problem as the causative agent of some diseases, such as lactose intolerance and galactosemia, or for being a by-product generated in huge amounts by the cheese industry.

Control of dinucleoside polyphosphates by the FHIT-homologous HNT2 gene, adenine biosynthesis and heat shock in Saccharomyces cerevisiae.

Background: The FHIT gene is lost early in the development of many tumors. Fhit possesses intrinsic ApppA hydrolase activity though ApppA cleavage is not required for tumor suppression. Because a mutant form of Fhit that is functional in tumor suppression and defective in catalysis binds ApppA well, it was hypothesized that Fhit-substrate complexes are the active, signaling form of Fhit.