Identification of the NC1 domain of {alpha}3 chain as critical for {alpha}3{alpha}4{alpha}5 type IV collagen network assembly.

ABSTRACT: The network organization of type IV collagen consisting of ?3, ?4, and ?5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual ?-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of ?3NC1 domain while keeping the triple helical ?3 chain intact by connecting it to the human ?5NC1 domain. The absence of ?3NC1 domain leads to the complete loss of the ?4 chain. The ?3 collagenous domain is incapable of incorporating the ?5 chain, resulting in the impaired organization of the ?3?4?5 chain-containing network. Although the ?5 chain can assemble with the ?1, ?2, and ?6 chains, such assembly is incapable of functionally replacing the ?3?4?5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.

SUBMITTER: LeBleu V 

PROVIDER: S-EPMC3009915 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature