Two Golgi-resident 3′-phosphoadenosine 5′-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans

Katsufumi Dejima, Daisuke Murata, Souhei Mizuguchi, Kazuko H. Nomura, Tomomi Izumikawa, Hiroshi Kitagawa, Keiko Gengyo-Ando, Sawako Yoshina, Tomomi Ichimiya, Shoko Nishihara, Shohei Mitani, Kazuya Nomura

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14 Citations (Scopus)

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- embryonicseamcelldevelopment,vulvalmorphogenesis,cell migration, and embryogenesis. The pst-2 mutant exhibited a wildtype 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.

Original languageEnglish
Pages (from-to)24717-24728
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number32
DOIs
Publication statusPublished - Aug 6 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Dejima, K., Murata, D., Mizuguchi, S., Nomura, K. H., Izumikawa, T., Kitagawa, H., Gengyo-Ando, K., Yoshina, S., Ichimiya, T., Nishihara, S., Mitani, S., & Nomura, K. (2010). Two Golgi-resident 3′-phosphoadenosine 5′-phosphosulfate transporters play distinct roles in heparan sulfate modifications and embryonic and larval development in Caenorhabditis elegans. Journal of Biological Chemistry, 285(32), 24717-24728. https://doi.org/10.1074/jbc.M109.088229