TRANSPORTERS OF NUCLEOTIDE SUGARS, ATP, AND NUCLEOTIDE SULFATE IN THEENDOPLASMIC-RETICULUM AND GOLGI-APPARATUS

The lumens of the endoplasmic reticulum and Golgi apparatus are the su bcellular sites where glycosylation, sulfation, and phosphorylation of secretory and membrane-bound proteins, proteoglycans, and lipids occu r, Nucleotide sugars, nucleotide sulfate, and ATP are substrates for t hese reactions. ATP is also used as an energy source in the lumen of t he endoplasmic reticulum during protein folding and degradation. The a bove nucleotide derivatives and ATP must first be translocated across the membrane of the endoplasmic reticulum and/or Golgi apparatus befor e they can serve as substrates in the above lumenal reactions. Translo cation of the above solutes is mediated for highly specific transporte rs, which are antiporters with the corresponding nucleoside monophosph ates as shown by biochemical and genetic approaches. Mutants in mammal s, yeast, and protozoa showed that a defect in a specific translocator activity results in selective impairments of the above posttranslatio nal modifications, including loss of virulence of pathogenic protozoa. Several of these transporters have been purl fled and cloned. Experim ents with yeast and mammalian cells demonstrate that these transporter s play a regulatory role in the above reactions. Future studies will a ddress the structure of the above proteins, how they are targeted to d ifferent organelles, their potential as drug targets, their role durin g development, and the possible occurrence of specific diseases.