We have established previously that the 67-kDa
elastin-binding protein (EBP), identical to the spliced variant of
beta-galactosidase, acts as a recyclable chaperone that facilitates secretion of
tropoelastin. (Hinek, A., Keeley, F. W., and Callahan, J. W. (1995) Exp. Cell Res. 220, 312-324). We now demonstrate that EBP also forms a cell surface-targeted molecular complex with protective
protein/
cathepsin A and
sialidase (neuraminidase-1), and provide evidence that this
sialidase activity is a prerequisite for the subsequent release of
tropoelastin. We found that treatment with
sialidase inhibitors repressed assembly of elastic fibers in cultures of human skin fibroblasts, aortic smooth muscle cells, and ear cartilage chondrocytes and caused impaired elastogenesis in developing chick embryos. Fibroblasts derived from patients with congenital
sialidosis (primary deficiency of
neuraminidase-1) and
galactosialidosis (secondary deficiency of
neuraminidase-1) demonstrated impaired elastogenesis, which could be reversed after their transduction with neuraminidase-1
cDNA or
after treatment with bacterial
sialidase, which has a similar substrate specificity to human neuraminidase-1. We postulate that neuraminidase-1 catalyzes removal of the terminal
sialic acids from
carbohydrate chains of microfibrillar
glycoproteins and other adjacent matrix
glycoconjugates, unmasking their penultimate galactosugars. In turn, the exposed galactosugars interact with the
galectin domain of EBP, thereby inducing the release of transported
tropoelastin molecules and facilitating their subsequent assembly into elastic fibers.