RRC ID 4337
Author Dejima K, Seko A, Yamashita K, Gengyo-Ando K, Mitani S, Izumikawa T, Kitagawa H, Sugahara K, Mizuguchi S, Nomura K.
Title Essential roles of 3'-phosphoadenosine 5'-phosphosulfate synthase in embryonic and larval development of the nematode Caenorhabditis elegans.
Journal J Biol Chem
Abstract Sulfation of biomolecules, which is widely observed from bacteria to humans, plays critical roles in many biological processes. All sulfation reactions in all organisms require activated sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), as a universal donor. In animals, PAPS is synthesized from ATP and inorganic sulfate by the bifunctional enzyme, PAPS synthase. In mammals, genetic defects in PAPS synthase 2, one of two PAPS synthase isozymes, cause dwarfism disorder, but little is known about the consequences of the complete loss of PAPS synthesis. To define the developmental role of sulfation, we cloned a Caenorhabditis elegans PAPS synthase-homologous gene, pps-1, and depleted expression of its product by isolating the deletion mutant and by RNA-mediated interference. PPS-1 protein exhibits specific activity to form PAPS in vitro, and disruption of the pps-1 gene by RNAi causes pleiotropic developmental defects in muscle patterning and epithelial cell shape changes with a decrease in glycosaminoglycan sulfation. Additionally, the pps-1 null mutant exhibits larval lethality. These data suggest that sulfation is essential for normal growth and integrity of epidermis in C. elegans. Furthermore, reporter analysis showed that pps-1 is expressed in the epidermis and several gland cells but not in neurons and muscles, indicating that PAPS in the neurons and muscles is provided by other cells.
Volume 281(16)
Pages 11431-40
Published 2006-4-21
DOI 10.1074/jbc.M601509200
PII S0021-9258(19)56321-9
PMID 16497669
MeSH Adenosine Triphosphate / chemistry Alleles Animals Body Patterning Caenorhabditis elegans Chondroitin Sulfates / metabolism Cloning, Molecular DNA, Complementary / metabolism Disaccharides / chemistry Electrophoresis, Polyacrylamide Gel Escherichia coli / metabolism Gene Deletion Gene Expression Regulation, Developmental* Genes, Reporter Glycosaminoglycans / metabolism Green Fluorescent Proteins / metabolism Microscopy, Fluorescence Models, Genetic Multienzyme Complexes / physiology* Muscles / metabolism Mutation Neurons / metabolism Phenotype Phosphoadenosine Phosphosulfate / chemistry RNA Interference Sulfate Adenylyltransferase / physiology* Temperature Transgenes
IF 4.238
Times Cited 18
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
C.elegans tm1109