RRC ID |
46705
|
Author |
Dejima K, Murata D, Mizuguchi S, Nomura KH, Izumikawa T, Kitagawa H, Gengyo-Ando K, Yoshina S, Ichimiya T, Nishihara S, Mitani S, Nomura K.
|
Title |
Two Golgi-resident 3'-Phosphoadenosine 5'-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans.
|
Journal |
J Biol Chem
|
Abstract |
Synthesis of extracellular sulfated molecules requires active 3'-phosphoadenosine 5'-phosphosulfate (PAPS). For sulfation to occur, PAPS must pass through the Golgi membrane, which is facilitated by Golgi-resident PAPS transporters. Caenorhabditis elegans PAPS transporters are encoded by two genes, pst-1 and pst-2. Using the yeast heterologous expression system, we characterized PST-1 and PST-2 as PAPS transporters. We created deletion mutants to study the importance of PAPS transporter activity. The pst-1 deletion mutant exhibited defects in cuticle formation, post-embryonic seam cell development, vulval morphogenesis, cell migration, and embryogenesis. The pst-2 mutant exhibited a wild-type phenotype. The defects observed in the pst-1 mutant could be rescued by transgenic expression of pst-1 and hPAPST1 but not pst-2 or hPAPST2. Moreover, the phenotype of a pst-1;pst-2 double mutant were similar to those of the pst-1 single mutant, except that larval cuticle formation was more severely defected. Disaccharide analysis revealed that heparan sulfate from these mutants was undersulfated. Gene expression reporter analysis revealed that these PAPS transporters exhibited different tissue distributions and subcellular localizations. These data suggest that pst-1 and pst-2 play different physiological roles in heparan sulfate modification and development.
|
Volume |
285(32)
|
Pages |
24717-28
|
Published |
2010-8-6
|
DOI |
10.1074/jbc.M109.088229
|
PII |
S0021-9258(20)66338-4
|
PMID |
20529843
|
PMC |
PMC2915708
|
MeSH |
Alleles
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins / physiology*
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation, Developmental*
Genes, Reporter
Glycosaminoglycans / chemistry
Golgi Apparatus / metabolism*
Green Fluorescent Proteins / chemistry
Heparitin Sulfate / metabolism*
Mutation
Nucleotide Transport Proteins / physiology*
Subcellular Fractions
Substrate Specificity
Transgenes
|
IF |
4.238
|
Times Cited |
12
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
C.elegans |
tm3364
tm3316 |