Control of the basement membrane and cell migration by ADAMTS proteinases: Lessons from C. elegans genetics

• Two ADAMTS proteinases MIG-17 and GON-1 act in C. elegans gonadogenesis.
• Mutations in fibulin-1 and type IV collagen suppress the mig-17 mutation.
• MIG-17 recruits nidogen to the BM in a fibulin-1- and type IV collagen-dependent manner.
• GON-1 and fibulin-1 act antagonistically in C. elegans gonadogenesis.

The members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of secreted proteins, MIG-17 and GON-1, play essential roles in Caenorhabditis elegans gonadogenesis. The genetic and molecular analyses of these proteinases uncovered novel molecular interactions regulating the basement membrane (BM) during the migration of the gonadal leader cells. MIG-17, which is localized to the gonadal BM recruits or activates fibulin-1 and type IV collagen, which then recruits nidogen, thereby inducing the remodeling of the BM that is required for directional control of leader cell migration. GON-1 acts antagonistically with fibulin-1 to regulate the levels of type IV collagen accumulation in the gonadal BM, which facilitates active migration of the leader cells. The cooperative action of MIG-17 and GON-1 represents an excellent model for understanding the mechanisms of organogenesis mediated by ADAMTS proteinases.