Three novel collagen VI chains, α4(VI), α5(VI), and α6(VI)

Abstract

We report the identification of three new collagen VI genes at a single locus on human chromosome 3q22.1. The three new genes are COL6A4, COL6A5, and COL6A6 that encode the α4(VI), α5(VI), and α6(VI) chains. In humans, the COL6A4 gene has been disrupted by a chromosome break. Each of the three new collagen chains contains a 336-amino acid triple helix flanked by seven N-terminal von Willebrand factor A-like domains and two (α4 and α6 chains) or three (α5 chain) C-terminal von Willebrand factor A-like domains. In humans, mRNA expression of COL6A5 is restricted to a few tissues, including lung, testis, and colon. In contrast, the COL6A6 gene is expressed in a wide range of fetal and adult tissues, including lung, kidney, liver, spleen, thymus, heart, and skeletal muscle. Antibodies to the α6(VI) chain stained the extracellular matrix of human skeletal and cardiac muscle, lung, and the territorial matrix of articular cartilage. In cell transfection and immunoprecipitation experiments, mouse α4(VI)N6-C2 chain co-assembled with endogenous α1(VI) and α2(VI) chains to form trimeric collagen VI molecules that were secreted from the cell. In contrast, α5(VI)N5-C1 and α6(VI)N6-C2 chains did not assemble with α1(VI) and α2(VI) chains and accumulated intracellularly. We conclude that the α4(VI)N6-C2 chain contains all the elements necessary for trimerization with α1(VI) and α2(VI). In summary, the discovery of three additional collagen VI chains doubles the collagen VI family and adds a layer of complexity to collagen VI assembly and function in the extracellular matrix. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.