Inositol and Phosphate Regulate
            <i>GIT1</i>
            Transcription and Glycerophosphoinositol Incorporation in
            <i>Saccharomyces cerevisiae</i>

Almaguer, Claudia; Mantella, D.; Perez, Evan; Patton‐Vogt, Jana

doi:10.1128/ec.2.6.1386.2003

Cited by 5 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among others, transcript levels of JEN1 which encodes a glucoserepressible lactate/pyruvate permease (Bojunga and Entian, 1999;Casal et al, 1999) was about 2-fold higher in HC42. We also noticed an activation of PHO84 encoding the high affinity phosphate permease (Bun-ya et al, 1991), which was expected due to the regulatory link between inositol and phosphate metabolism (Almaguer et al, 2003), and a 2 -fold upregulation of SLT1 encoding the glycerol/H + symporter (Ferreira et al, 2005). The latter activation may be a consequence of the increased osmotic potential of the cytoplasm due to intracellular accumulation of glycerol.…”

Section: Article In Pressmentioning

confidence: 57%

A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production

Cordier

Mendes

Vasconcelos

et al. 2007

Metabolic Engineering

View full text Add to dashboard Cite

Towards a global objective to produce chemical derivatives by microbial processes, this work dealt with a metabolic engineering of the yeast Saccharomyces cerevisiae for glycerol production. To accomplish this goal, overexpression of GPD1 was introduced in a tpi1delta mutant defective in triose phosphate isomerase. This strategy alleviated the inositol-less phenotype of this mutant, by reducing the levels of dihydroxyacetone phosphate and glycerol-3-P, two potent inhibitors of myo-inositol synthase that catalyzes the formation of inositol-6-phosphate from glucose-6-phosphate. Further deletion of ADH1 and overexpression of ALD3, encoding, respectively, the major NAD+-dependent alcohol dehydrogenase and a cytosolic NAD+-dependent aldehyde dehydrogenase yielded a yeast strain able to produce 0.46 g glycerol (g glucose)(-1) at a maximal rate of 3.1 mmol (g dry mass)(-1) h(-1) in aerated batch cultures. At the metabolic level, this genetic strategy shifted the flux control coefficient of the pathway to the level of the glycerol efflux, with a consequent intracellular accumulation of glycerol that could be partially reduced by the overproduction of glycerol exporter encoded by FPS1. At the transcriptomic level, this metabolic reprogramming brought about the upregulation of genes encoding NAD+/NADP+ binding proteins, a partial derepression of genes coding for TCA cycle and respiratory enzymes, and a downregulation of genes implicated in protein biosynthesis and ribosome biogenesis. Altogether, these metabolic and molecular alterations stand for major hurdles that may represent potential targets for further optimizing glycerol production in yeast.

show abstract

Section: Article In Pressmentioning

confidence: 57%

A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production

Cordier

Mendes

Vasconcelos

et al. 2007

Metabolic Engineering

View full text Add to dashboard Cite

show abstract

“…No alteration in Gro P Ins metabolism is observed in either the YPL110c or YPL206c mutant strains, which suggests another gene that remains to be identified should determine the metabolic fate of Gro P Ins . However, the evidence that Gro P Ins can be used as a phosphate and inositol source suggests that there should be an enzyme with Gro P Ins phosphodiesterase activity .…”

Section: Saccharomyces Cerevisiae Gp‐pdesmentioning

confidence: 97%

The emerging physiological roles of the glycerophosphodiesterase family

et al. 2014

View full text Add to dashboard Cite

The glycerophosphodiester phosphodiesterases are evolutionarily conserved proteins that have been linked to several patho/physiological functions, comprising bacterial pathogenicity and mammalian cell proliferation or differentiation. The bacterial enzymes do not show preferential substrate selectivities among the glycerophosphodiesters, and they are mainly dedicated to glycerophosphodiester hydrolysis, producing glycerophosphate and alcohols as the building blocks that are required for bacterial biosynthetic pathways. In some cases, this enzymatic activity has been demonstrated to contribute to bacterial pathogenicity, such as with Hemophilus influenzae. Mammalian glyerophosphodiesterases have high substrate specificities, even if the number of potential physiological substrates is continuously increasing. Some of these mammalian enzymes have been directly linked to cell differentiation, such as GDE2, which triggers motor neuron differentiation, and GDE3, the enzymatic activity of which is necessary and sufficient to induce osteoblast differentiation. Instead, GDE5 has been shown to inhibit skeletal muscle development independent of its enzymatic activity.

show abstract

“…Once internalized, GPI is eventually broken down into inositol, phosphate and glycerol, thus contributing to the cellular pool of these metabolites (Patton-Vogt and Henry, 1998). In fact, Git1 was first cloned for its ability to restore growth to the inositol auxotroph, ino1 , which harbors a mutation in inositol-1-phosphate synthase (Patton-Vogt and Henry, 1998), demonstrating that uptake of GPI through Git1 provides inositol to cells (Almaguer et al ., 2003; Almaguer et al ., 2004). Not surprisingly, transcription of the GIT1 gene is regulated by inositol, and more exquisitely by phosphate (Almaguer et al ., 2003; Almaguer et al ., 2004).…”

Section: Introductionmentioning

confidence: 99%

“…In fact, Git1 was first cloned for its ability to restore growth to the inositol auxotroph, ino1 , which harbors a mutation in inositol-1-phosphate synthase (Patton-Vogt and Henry, 1998), demonstrating that uptake of GPI through Git1 provides inositol to cells (Almaguer et al ., 2003; Almaguer et al ., 2004). Not surprisingly, transcription of the GIT1 gene is regulated by inositol, and more exquisitely by phosphate (Almaguer et al ., 2003; Almaguer et al ., 2004). The GIT1 promoter contains binding sites for the transcription factors Pho2 and Pho4 (Almaguer et al ., 2004), which respond to phosphate limitation by co-operatively binding to the promoters of genes encoding proteins needed for phosphate uptake and/or scavenging (Vogel et al ., 1989; Magbanua et al ., 1997; Shao et al ., 1998).…”

Section: Introductionmentioning

confidence: 99%

Alpha-arrestins Aly1 and Aly2 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis

Robinson

Hawbaker

Chiang

et al. 2021

Preprint

View full text Add to dashboard Cite

Phosphatidylinositol (PI) is an essential phospholipid and critical component of membrane bilayers. The complete deacylation of PI by phospholipases of the B-type leads to the production of intracellular and extracellular glycerophosphoinositol (GPI), a water-soluble glycerophosphodiester. Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters that resides at the plasma membrane in yeast. Once internalized, GPI can be degraded to produce inositol, phosphate and glycerol, thereby contributing to reserves of these building blocks. Not surprisingly, GIT1 gene expression is controlled by nutrient balance, with limitation for phosphate or inositol each increasing GIT1 expression to facilitate GPI uptake. Less is known about how Git1 protein levels or localization are controlled. Here we show that the α-arrestins, an important class of protein trafficking adaptor, regulate the localization of Git1 in a manner dependent upon their association with the ubiquitin ligase Rsp5. Specifically, α-arrestin Aly2 is needed for effective Git1 internalization from the plasma membrane under basal conditions. However, in response to GPI-treatment of cells, either Aly1 or Aly2 can promote Git1 trafficking to the vacuole. Retention of Git1 at the cell surface, as occurs in aly1∆ aly2∆ cells, results in impaired growth in the presences of excess exogenous GPI and results in increased uptake of radiolabeled GPI, suggesting that accumulation of this metabolite or its downstream products leads to cellular toxicity. We further show that regulation of α-arrestin Aly1 by the protein phosphatase calcineurin improves both steady-state and ligand-induced trafficking of Git1 when a mutant allele of Aly1 that mimics the dephosphorylated state at calcineurin-regulated residues is employed. Thus, calcineurin regulation of Aly1 is important for the GPI-ligand induced trafficking of Git1 by this α-arrestin, however, the role of calcineurin in regulating Git1 trafficking is much broader than can simply be explained by regulation of the α-arrestins. Finally, we find that loss of Aly1 and Aly2 leads to an increase in phosphatidylinositol-3-phosphate on the limiting membrane of the vacuole and this alteration is further exacerbated by addition of GPI, suggesting that the effect is at least partially linked to Git1 function. Indeed, loss of Aly1 and Aly2 leads to increased incorporation of inositol label from 3H-inositol-labelled GPI into PI, confirming that internalized GPI influences PI synthesis and indicating a role for the α-arrestins in regulating the process.

show abstract

Inositol and Phosphate Regulate GIT1 Transcription and Glycerophosphoinositol Incorporation in Saccharomyces cerevisiae

Cited by 5 publications

References 0 publications

A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production

A metabolic and genomic study of engineered Saccharomyces cerevisiae strains for high glycerol production

The emerging physiological roles of the glycerophosphodiesterase family

Alpha-arrestins Aly1 and Aly2 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis

Contact Info

Product

Resources

About