Nanomelic chondrocytes synthesize a glycoprotein related to chondroitin sulfate proteoglycan core protein.

Abstract

Chicken embryos homozygous for the autosomal recessive gene nanomelia exhibit cartilage defects, synthesize low levels of cartilage chondroitin sulfate proteoglycan (CSPG), and are missing the CSPG core protein (Argraves, W. S., McKeown-Longo, P. J., and Goetinck, P. F. (1981) FEBS Lett. 131, 265). In our studies of nanomelic chondrocytes in culture, we detected neither sulfate-labeled CSPG nor its Mr 370,000 core protein. However, in immunoprecipitation reactions using both polyclonal and monoclonal antibodies directed against the cartilage CSPG core protein, we identified a protein of Mr 300,000 that contains an epitope found in the hyaluronic acid-binding region of the normal core protein. This protein was also detected among products synthesized by chondrocytes obtained from phenotypically normal embryos resulting from matings between parents heterozygous for nanomelia. Sensitivity to endoglycosidase H indicated that the product is a glycoprotein with attached mannose-rich oligosaccharides. Pulse-chase studies revealed the disappearance of the glycoprotein after 6 h of chase, but no detectable formation of proteoglycan. Our results suggest that although nanomelic chondrocytes are deficient in the production of normal CSPG and its core protein, they do synthesize a smaller, immunologically related glycoprotein that does not undergo the post-translational processing characteristic of the normal cartilage core protein.