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Figure 5. Model of SPARC acting as a collagen chaperone. Molecular chaperones and folding enzymes ensure that secretory proteins are correctly folded into their native state prior to exiting the endoplasmic reticulum. The unique and complex folding and assembly of procollagen 
-chains into triple-helical collagen molecules are orchestrated by several endoplasmic reticulum resident molecular chaperones, including the collagen-specific chaperone HSP47. Analysis of the data indicates that the amino acids essential for the Ca2+-binding of SPARC to collagens are evolutionarily conserved in organisms ranging from nematodes to mammals. Studies in Drosophila have indicated that SPARC expression is required for the deposition of collagen IV in basal laminae by hemocytes during embryonic development. We hypothesize that, in invertebrates that do not code for HSP47, intracellular SPARC functions as the principal collagen-specific molecular chaperone, stabilizing triple helices prior to their export from the endoplasmic reticulum. We further hypothesize that SPARC may also promote the assembly and maturation of collagen fibrils by regulating the binding of molecules, such as decorin, which bind directly to collagens and inhibit fibrillogenesis. The latter may, in part, account for the smaller fibrils in SPARC-null mice.
