SUMMARY PARAGRAPH for ERS1
ERS1 encodes an endosomal and vacuolar-localized seven transmembrane domain-containing cystine transporter (1, 3). Cystine, the disulfide-linked form of cysteine, is generated as a byproduct of protein hydrolysis in the vacuole, and must be exported to the cytoplasm where it is reduced to cysteine. ERS1 was originally isolated as a suppressor of an ERD1 mutation (1). ERD1 mutants are defective in the HDEL tetrapeptide-mediated retrieval and retention of lumenal endoplasmic reticulum (ER) proteins, and are also defective in Golgi-dependent glycoprotein processing (4). ERS1 deletion mutants are viable and display hygromycin B sensitivity but are not defective in the retention of ER proteins (1, 3). MEH1, a gene involved in vacuolar acidification and positive regulation of microautophagy, has been identified as a high-copy number suppressor of an ERS1 deletion (3).
Cystinosin, a lysosomal H(+)-driven cystine transporter encoded by the CTNS (OMIM) locus in humans is a functional homolog of Ers1p (3, 2). The human cystinosin symporter is responsible for the export of cystine from lysosomes (2). Mutations in the CTNS gene result in several related cystinotic disorders including nephropathic cystinosis, a lysosomal storage disease characterized by the accumulation of cystine crystals in various organs including the eyes, kidneys, and liver (5). This disorder presents clinically as renal Fanconi Syndrome (OMIM), a failure of the kidneys to reabsorb nutrients and minerals that results in end-stage kidney failure (5). A strong correlation exists between the clinical severity associated with various CTNS mutant alleles identified in cystinosis patients and the degree with which these mutant alleles are able to complement an ERS1 deletion strain (3).
Last updated: 2007-02-14