Mammalian collagen IV

Abstract

Four decades have passed since the first discovery of collagen IV by Kefalides in 1966. Since then collagen IV has been investigated extensively by a large number of research laboratories around the world. Advances in molecular genetics have resulted in identification of six evolutionary related mammalian genes encoding six different polypeptide chains of collagen IV. The genes are differentially expressed during the embryonic development, providing different tissues with specific collagen IV networks each having unique biochemical properties. Newly translated α-chains interact and assemble in the endoplasmic reticulum in a chain-specific fashion and form unique heterotrimers. Unlike most collagens, type IV collagen is an exclusive member of the basement membranes and through a complex inter-and intramolecular interactions form supramolecular networks that influence cell adhesion, migration, and differentiation. Collagen IV is directly involved in a number of genetic and acquired disease such as Alport's and Goodpasture's syndromes. Recent discoveries have also highlighted a new and direct role for collagen IV in the development of rare genetic diseases such as cerebral hemorrhage and porencephaly in infants and hemorrhagic stroke in adults. Years of intensive investigations have resulted in a vast body of information about the structure, function, and biology of collagen IV. In this review article, we will summarize essential findings on the structural and functional relationships of different collagen IV chains and their roles in health and disease.

Breakpoint determination of X;autosome balanced translocations in four patients with premature ovarian failure

“…The chains interact and assemble with specificity to form three distinct patterns: a1a1a2, a3a4a5 and a5a5a6. 11 The a5-and a6-chains are found in the basement membrane of skin, smooth muscle and kidney. 12 Two transcripts of COL4A6 are known, isoforms A and B (Figure 3b).…”

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

“…Using IHC analysis, we found variable IGF-IR levels in clinical specimens of hepatic metastases that did not always correlate with collagen IV levels (data not shown). Although the regulation of collagen IV gene expression is not yet fully understood (Khoshnoodi et al, 2008), several factors have been identified, including high glucose levels, transforming growth factor-b1 (Iglesias-de la Cruz et al, 2002), hypoxia via the hypoxia-inducible factor (HIF)-1a (Steenhard et al, 2010) and the tumor-suppressor von Hippel-Lindau that in addition to its role in regulating HIF-1a levels was also implicated in the assembly of collagen IV matrix (Kurban et al, 2008). Some of these factors have also been shown to play important roles during the early stages of liver metastasis (VidalVanaclocha, 2008).…”

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature

“…The C-terminal NC1 domain is important in the initiation of triple helix formation. [23][24][25] Mice harboring heterozygous mutations in Col4a1 or Col4a2 suffer from hemorrhage in the eye, brain, and skin, which already occur during gestation and sometimes lead to developmental defects of the eye and brain. Therefore, similarities in phenotypes between COL4A1 and COL4A2 mutations were to be expected.…”