The folded protein modules of the C-terminal G3 domain of aggrecan can each facilitate the translocation and secretion of the extended chondroitin sulfate attachment sequence

Aggrecan is a multidomain proteoglycan containing both extended and folded protein modules. The C-terminal G3 domain contains a lectin-like, complemen t regulatory protein-like, and two alternatively spliced epidermal growth f actor-like modules. It has been proposed that the lectin module alone has a necessary role in the intracellular translocation and secretion of protein s expressed containing G3. Constructs containing human aggrecan G3 together with 1155 bases of the adjacent chondroitin sulfate attachment region (CS- 2) were prepared with different combinations and deletions of the protein m odules and transfected into mammalian cells of monkey or hamster origin. Th e results showed that the products containing only the unfolded protein seq uences (CS-2 with or without the C-terminal tail sequence) were translated and accumulated intracellularly but were not secreted. In contrast the cons tructs containing any of the folded protein modules and the extended CS-2 r egion were translated and secreted from the cells. The results show that th e lectin module was not unique in facilitating the intracellular translocat ion and secretion of the G3 domain. The conservation of G3-like domains wit hin the aggrecan family of proteoglycans may therefore result from their pa rticipation in other extracellular functions.