The subcellular PAPS synthesis pathway responsible for the sulfation of proteoglycans: A comparison between humans and Drosophila melanogaster

Abstract

Proteoglycans (PGs) are molecules found in abundance on the cell surface and in the extracellular matrix, and are involved in a variety of biological phenomena. A recent analysis of Drosophila melanogaster mutants with defects in sulfotransferases revealed the significance of sulfation of Glycosaminoglycans (GAGs) on growth factor signaling during development. Sulfation of GAGs requires four steps: i) active transport of sulfate ion into the cells by sulfate transporters, ii) conversion into 3′-phosphoadenosine 5′- phosphosulfate (PAPS) by PAPS synthases, iii) translocation of PAPS from the cytosol into the Golgi apparatus by a PAPS transporter, and iv) transfer of sulfate from PAPS to GAGs by sulfotransferases. The components of these steps are conserved among vertebrate and invertebrate animals. In this review, we summarize the significance of each step in providing PAPS prior to sulfotransferases, by comparing human and Drosophila genes.