Drosophila Golgi protein, Rotini, regulates glycosaminoglycan chains polymerases in the biogenesis of Heparan Sulfate Proteoglycans
Date Issued
2007
Date
2007
Author(s)
Chang, Che-Wei
Abstract
Heparan sulfate proteoglycans (HSPGs) are components of ECM and critical to distribution and signaling of Hedgehog (Hh), Wingless (Wg) and Decapentaplegic (Dpp) morphogens in Drosophila. Mutations in HSPGs core proteins and in enzymes required for heparan sulfate glycosaminoglycan (HS GAG) chain synthesis will lead to reduction of morphogens expression and aberrant signaling. ere we report that Rotini (Rti), a Drosophila homologue of human GPP34 protein, can regulate expression and signaling of morphogens, such as Hedgehog (Hh). Further studies indicate that Rti affects Hh behaviors by mediating HSPGs expression but not directly regulates Hh transcription, translation and autocleavage process. oreover, a v-SNARE protein, dVti1, involved in Golgi retrograde trafficking in yeast is identified to physically interact with Rti through yeast two-hybrid screen, and this interaction is further confirmed by GST pull down assay. Rti and dVti1 are partially colocalized in Drosophila S2 cells and wing disc cells. Genetically, overexpression of dVti1 can suppress the reduction of HSPGs caused by rti mutation. hese results suggest that Rti and dVti1 are the two directly interacting components involved in mechanism of HSPGs biogenesis. ti is not required for expression of HSPGs core protein, Dally-like protein (Dlp), and, secretion of Dlp to cell surface is either not affected in rti mutant cells. Rti is involved in formation of HS GAG chain by regulating GAG chain polymerases, EXT protein family; however, Rti is not required for expressions of Sulfateless (Sfl) and Slalom (Sll), which are involved in sulfation on GAG chains.ased on these finding, we propose that Rti and dVti1 are involved in the trafficking process of EXT proteins in Golgi complex to regulate the polymerization of GAG chains and biogenesis of HSPGs.
Subjects
Hh
HSPGs
GPP34
EXT
vesicle transport
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