[Metabolism of heparan sulfate proteoglycans in Drosophila cell lines]

Proteoglycans with glycosaminoglycan side chains are found on the cell surface and in the extracellular matrix. Recently, it has been demonstrated that they are widely distributed in invertebrates, as well as in vertebrates. In the fruit fly, Drosophila melanogaster, core proteins of heparan sulfate proteoglycans (HSPGs), including division abnormally delayed (dally), dally-like, perlecan, and syndecan, have been identified by genetic analyses. Biochemical studies of the glycosaminoglycan structure in Drosophila have also found the presence of chondroitin sulfate, in addition to heparin sulfate; however, its core protein remains to be identified. Functional studies of HSPG in Drosophila have shown that dally and dally-like (members of glypican) are required for Wingless (a member of the Wnt family) signaling, and they are also implicated in affecting signaling of Decapentaplegic (a member of the transforming growth factor-beta/bone morphogenetic protein superfamily). Further evidence that HSPGs play important roles in these cellular signaling processes has been established from studies of genetic mutants defective in biosynthetic enzymes of HSPGs, such as sugarless (a homologue of UDP dehydrogenase), sulfateless (a homologue of HS N-deacetylase/N-sulfotransferase), and tout-velu (a homologue of Ext encoding HS polymerase). In this paper, the metabolism of Drosophila HSPGs was investigated to further clarify their biological functions, in two Drosophila cell lines: S 2 cell and Kc cell, using metabolic labeling techniques in combination with various pulse-chase protocols.