Organization and Expression of Basement Membrane Collagen IV

Six distinct genes have been identified as belonging to the type IV collagen gene family. They can be organized into three sets, i.e., COL4A1/COL4A2, COL4A3/COL4A4, and COL4A5/COL4A6, which are localized on three different chromosomes in humans, 13,2, and X, respectively. Within each set the genes are aligned head-to-head and their expression is regulated by bidirectional promoters between the genes. Transcriptional regulation of the COL4A1/COL4A2 set has been well characterized. The transcription of C0L4A6 seems to be controlled by two alternative promoters. While collagen IV molecules composed of a l and a.2 chains are broadly distributed, molecules comprising combinations of the other four chains, a3-a6, are important components of specialized basement membranes. The precise chain composition of triple-helical molecules assembled from the a3-cc6 chains is not entirely clear, but it is hypothesized that «3-«5 chains and «5 and «6 chains form heterotrimeric molecules. Several pieces of evidence indicate that aS/a4/a5 molecules and a5/a6 molecules are components of the basement membrane network. This helps explain the observation that the kidney and skin basement membranes from patients with Alport syndrome caused by mutations in the «5 coding gene, COL4A5, are defective in the aS, «4