27.11: Type IV Collagen of Basal Lamina

Type IV collagen is a 400 nm long, network-forming collagen that acts as a barrier between the epithelial and endothelial cells. Type IV collagen forms the backbone of the basement membrane by scaffolding with laminin, entactin, proteoglycans, and fibronectin. Apart from rendering structural support to the basement membrane, it also helps entail signaling potentials necessary for both pathological and physiological functions.

A type IV collagen molecule has six alpha chains which can exist in at least three hetero-trimeric triple helical configurations viz. [α1(IV)]2α2(IV), [α3(IV)]2α4(IV), and [α5(IV)]2α6(IV). The alpha chain is composed of a cysteine-rich N-terminal S-domain, a long triple helical domain with Gly–X–Y repeats, and a globular C-terminal domain containing approximately 230 amino acids. These collagen fibers can either form a dimer via head-to-head interactions or a tetramer via tail-to-tail interactions.

Mutation of the genes responsible for coding type IV collagen, such as COL4A5, can lead to Alport syndrome. In this syndrome, the glomerular basement membrane thins and eventually forms fissures. This disease is characterized by kidney problems, hearing loss, and eye abnormalities. Excessive deposition of collagen IV in the liver may lead to liver fibrosis and cirrhosis. The inflammation of liver cells activates the Kupffer cells to release fibrogenic mediators, which eventually results in increased secretion of extracellular matrix proteins.

Type IV collagens are non-fibrillar or network-forming collagens which are primarily found in the basal lamina.

A typical type IV collagen is a 400 nm long, triple-helical structure interrupted by several non-helical regions which add flexibility to the molecule.

At the N-terminal, it has a small globular domain, while a large globular domain is present at the C-terminal.

Through these terminal globular domains, the collagen fibres can associate with each other by head-to-head interactions forming a dimer; and tail-to-tail interactions forming a tetramer. The fibres also associate by lateral interactions between the triple-helical regions. 

Such complex associations can form a two dimensional, irregular network, which provides tensile strength to the basal lamina.

This network further links with the laminin lattice and other glycoproteins such as perlecan and entactin,  to build a complete basal lamina.