The phospholipase-mediated deacylation of phosphatidylinositol (P1) to produce extracellular glycerophosphoinositol (GroPIns) is a major catabolic pathway in S. cerevisiae cells grown in inositolcontaining medium. In times of inositol limitation, GroPlns is transported back into the cell in an energy requiring process mediated by the product of the GIT1 gene. This novel membrane permease has a number of interesting features that make it worthy of intensive study. Gitip is the first GroPlns transporter to be characterized in any organism, and there is evidence for the existence of such a transporter in higher eukaryotes. The GroPlns transported through Gitlp is used for the synthesis of PT and its inositol-containing derivatives, many of which play important roles in signal transduction. Thus, the activity of Gitip may impinge upon a number of important cellular events. In addition, evidence suggesting that the transport of GroPlns through Gitip is regulated by both phospholipid metabolism and phosphate metabolism raises the prospect of characterizing the regulatory networks linking these two fundamental aspects of cellular metabolism by means of the study of Gitip. Finally, the unique chromosomal location of GIT1 provides an opportunity to study the role of transcriptional silencing in regulating GIT1 expression.
The Specific Aims of this proposal are to examine the regulation of GroPlns transport through Gitip at the transcriptional and posttranslational levels by 1) phospholipid metabolism, 2) the Unfolded Protein Response Pathway, 3) phosphate metabolism ,and 4) gene location.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059817-04
Application #
6659769
Study Section
Physiological Chemistry Study Section (PC)
Program Officer
Chin, Jean
Project Start
2001-02-01
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$215,306
Indirect Cost
Name
Duquesne University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004501193
City
Pittsburgh
State
PA
Country
United States
Zip Code
15282
Bishop, Andrew C; Surlow, Beth A; Anand, Puneet et al. (2009) Neurofibromin homologs Ira1 and Ira2 affect glycerophosphoinositol production and transport in Saccharomyces cerevisiae. Eukaryot Cell 8:1808-11
Simockova, Maria; Holic, Roman; Tahotna, Dana et al. (2008) Yeast Pgc1p (YPL206c) controls the amount of phosphatidylglycerol via a phospholipase C-type degradation mechanism. J Biol Chem 283:17107-15
Nunez, Lilia R; Jesch, Stephen A; Gaspar, Maria L et al. (2008) Cell wall integrity MAPK pathway is essential for lipid homeostasis. J Biol Chem 283:34204-17
Patton-Vogt, Jana (2007) Transport and metabolism of glycerophosphodiesters produced through phospholipid deacylation. Biochim Biophys Acta 1771:337-42
Matsuo, Yasuhiro; Fisher, Edward; Patton-Vogt, Jana et al. (2007) Functional characterization of the fission yeast phosphatidylserine synthase gene, pps1, reveals novel cellular functions for phosphatidylserine. Eukaryot Cell 6:2092-101
Almaguer, Claudia; Fisher, Edward; Patton-Vogt, Jana (2006) Posttranscriptional regulation of Git1p, the glycerophosphoinositol/glycerophosphocholine transporter of Saccharomyces cerevisiae. Curr Genet 50:367-75
Fisher, Edward; Almaguer, Claudia; Holic, Roman et al. (2005) Glycerophosphocholine-dependent growth requires Gde1p (YPL110c) and Git1p in Saccharomyces cerevisiae. J Biol Chem 280:36110-7
Almaguer, Claudia; Cheng, Wei; Nolder, Christi et al. (2004) Glycerophosphoinositol, a novel phosphate source whose transport is regulated by multiple factors in Saccharomyces cerevisiae. J Biol Chem 279:31937-42
Almaguer, C; Mantella, D; Perez, E et al. (2003) Inositol and phosphate regulate GIT1 transcription and glycerophosphoinositol incorporation in Saccharomyces cerevisiae. Eukaryot Cell 2:729-36
Dowd, S R; Bier, M E; Patton-Vogt, J L (2001) Turnover of phosphatidylcholine in Saccharomyces cerevisiae. The role of the CDP-choline pathway. J Biol Chem 276:3756-63