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Original Paper

Free Access

Identification of Human Gene Products Containing Pro-Pro-x-Tyr (PY) Motifs that Enhance Glutathione and Endocytotic Marker Uptake in Yeast

Shi S.1,* · Notenboom S.1,* · Dumont M.E.2 · Ballatori N.1

Author affiliations

Departments of 1Environmental Medicine,2and Biochemistry and Biophysics, University of Rochester School of Medicine, Rochester,*Contributed equally to the results of this article

Corresponding Author

Ned Ballatori, Ph.D.

Box EHSC, 601 Elmwood Ave, Rochester, NY 14642 (USA)

Tel. + 1 585-275-0262, Fax: + 1 585-256-2591

E-Mail Ned_Ballatori@urmc.rochester.edu

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Cell Physiol Biochem 2010;25:293–306

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In an attempt to identify genes involved in glutathione (GSH) transport, a human mammary gland cDNA library was screened for clones capable of complementing a defect in GSH uptake in yeast cells that lack Hgt1p, the primary yeast GSH uptake transporter. Five genes capable of rescuing growth on sulfur-deficient GSH-containing medium were identified: prostate transmembrane protein, androgen induced 1 (PMEPA1); lysosomal-associated protein transmembrane 4 alpha (LAPTM4α); solute carrier family 25, member 1 (SLC25A1); lipopolysaccharide-induced TNF factor (LITAF); and cysteine/tyrosine-rich-1 (CYYR1). All of these genes encode small integral membrane proteins of unknown function, although none appear to encode prototypical GSH transporters. Nevertheless, they all increased both intracellular glutathione levels and [3H]GSH uptake rates. [3H]GSH uptake was uniformly inhibited by high concentrations of unlabeled GSH, GSSG, and ophthalmic acid. Interestingly, each protein is predicted to contain Pro-Pro-x-Tyr (PY) motifs, which are thought to be important for regulating protein cell surface expression. Uptake of the endocytotic markers lucifer yellow and FM4-64 was also enhanced by each of the five genes. Mutations of the PY motifs in LITAF largely abolished all of its effects. In summary, although the results do not reveal novel GSH transporters, they identify five PY-containing human gene products that may influence plasma membrane transport activity.

© 2010 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: November 19, 2009
Published online: January 12, 2010
Issue release date: January 2010

Number of Print Pages: 14
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

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