title: Disruption of a cystine transporter downregulates expression of genes involved in sulfur regulation and cellular respiration.
abstract: Cystine and cysteine are important molecules for pathways such as redox signaling and regulation, and thus identifying cellular deficits upon deletion of the Saccharomyces cerevisiae cystine transporter Ers1p allows for a further understanding of cystine homeostasis. Previous complementation studies using the human ortholog suggest yeast Ers1p is a cystine transporter. Human CTNS encodes the protein Cystinosin, a cystine transporter that is embedded in the lysosomal membrane and facilitates the export of cystine from the lysosome. When CTNS is mutated, cystine transport is disrupted, leading to cystine accumulation, the diagnostic hallmark of the lysosomal storage disorder cystinosis. Here, we provide biochemical evidence for Ers1p-dependent cystine transport. However, the accumulation of intracellular cystine is not observed when the ERS1 gene is deleted from ers1-Δ yeast, supporting the existence of modifier genes that provide a mechanism in ers1-Δ yeast that prevents or corrects cystine accumulation. Upon comparison of the transcriptomes of isogenic ERS1+ and ers1-Δ strains of S. cerevisiae by DNA microarray followed by targeted qPCR, sixteen genes were identified as being differentially expressed between the two genotypes. Genes that encode proteins functioning in sulfur regulation, cellular respiration, and general transport were enriched in our screen, demonstrating pleiotropic effects of ers1-Δ. These results give insight into yeast cystine regulation and the multiple, seemingly distal, pathways that involve proper cystine recycling.
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Simpkins
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Kirby E
authors.initials: KE
authors.lastname: Rickel
authors.affiliation: Sanford Research Children's Health Research Center, Sioux Falls, SD, USA 57104.
authors.forename: Marianna
authors.initials: M
authors.lastname: Madeo
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Bethany A
authors.initials: BA
authors.lastname: Ahlers
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Gabriel B
authors.initials: GB
authors.lastname: Carlisle
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Nelson
authors.affiliation: Sanford Research Children's Health Research Center, Sioux Falls, SD, USA 57104.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Cardillo
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Weber
authors.affiliation: Sanford Research Children's Health Research Center, Sioux Falls, SD, USA 57104.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Vitiello
authors.affiliation: Sanford Research Children's Health Research Center, Sioux Falls, SD, USA 57104.
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
authors.affiliation: Biology Department, Augustana University, Sioux Falls, SD, USA 57197 seasson.vitiello@augie.edu.
authors.forename: Seasson P
authors.identifier: http://orcid.org/0000-0001-5817-4685
authors.initials: SP
authors.lastname: Vitiello
keywords: CTNS; Cystine; ERS1