Assembly of Type IV Collagen

Abstract

Type IV collagen includes six genetically distinct polypeptides named ␣1(IV) through ␣6(IV). These iso-forms are speculated to organize themselves into unique networks providing mammalian basement membranes specificity and inequality. Recent studies using bovine and human glomerular and testis basement membranes have shown that unique networks of collagen compris-ing either ␣1 and ␣2 chains or ␣3, ␣4, and ␣5 chains can be identified. These studies have suggested that assem-bly of ␣5 chain into type IV collagen network is depend-ent on ␣3 expression where both chains are normally present in the tissue. In the present study, we show that in the lens and inner ear of normal mice, expression of ␣1, ␣2, ␣3, ␣4, and ␣5 chains of type IV collagen can be detected using ␣ chain-specific antibodies. In the ␣3(IV) collagen-deficient mice, only the expression of ␣1, ␣2, and ␣5 chains of type IV collagen was detectable. The non-collagenous 1 domain of ␣5 chain was associated with ␣1 in the non-collagenous 1 domain hexamer struc-ture, suggesting that network incorporation of ␣5 is pos-sible in the absence of the ␣3 chain in these tissues. The present study proves that expression of ␣5 is not de-pendent on the expression of ␣3 chain in these tissues and that ␣5 chain can assemble into basement mem-branes in the absence of ␣3 chain. These findings sup-port the notion that type IV collagen assembly may be regulated by tissue-specific factors. Type IV collagen is a family of complex polypeptides and a major constituent of mammalian basement membranes (1, 2). The ␣1(IV) and ␣2(IV) chains are products of distinct genes located pairwise in a head-to-head fashion on chromosome 13 in humans (3). The ␣3(IV) and ␣4(IV) chains are present in the same orientation on chromosome 2, and the ␣5(IV) and ␣6(IV) chains are located on the X chromosome in humans (4). The type IV collagen protomer (trimer) consists of three ␣ chains that come together through associations among their NC1 1