COLLAGEN-XVIII IS A BASEMENT-MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN

The present study shows that collagen XVIII is, next to perlecan and a grin, the third basal lamina heparan sulfate proteoglycan (HSPG) and t he first collagen/proteoglycan with heparan sulfate side chains. By us ing monoclonal antibodies to an unidentified HSPG in chick, 14 cDNA cl ones were isolated from a chick yolk sac library. All clones had a com mon nucleotide sequence that was homologous to the mRNA sequences of m ouse and human collagen XVIII. The deduced amino acid sequence of the chick fragment shows an 83% overall homology with the human and mouse collagen XVIII. Similar to the human and mouse homologue, the chick co llagen XVIII mRNA has a size of 4.5 kilobase pairs. In Western blots, collagen XVIII appeared as a smear with a molecular mass of 300 kDa. A fter treatment with heparitinase, the protein was reduced in molecular mass by 120 kDa to a protein core of 180 kDa. Collagen XVIII has typi cal features of a collagen, such as its existence, under nondenaturing conditions, as a non-covalently linked oligomer, and a sensitivity of the core protein to collagenase digestion. It also has characteristic s of an HSPG, such as long heparitinase-sensitive carbohydrate chains and a highly negative net charge. Collagen XVIII is abundant in basal laminae of the retina, epidermis, pia, cardiac and striated muscle, ki dney, blood vessels, and lung. In situ hybridization showed that the m ain expression of collagen XVIII: HSPG in the chick embryo is in the k idney and the peripheral nervous system. As a substrate, collagen XVII I moderately promoted the adhesion of Schwann cells but had no such ac tivity on peripheral nervous system neurons and axons.