Binding of microfibril‐associated glycoprotein 2 to extracellular microfibrils is promoted by proprotein convertase cleavage (1005.3)

Abstract

Microfibrils are extracellular matrix fibers whose major components are the fibrillin proteins (Fbn‐1, ‐2, ‐3), which are important for tissue mechanical stability and elasticity. MAGP2 is a secreted protein found on specific microfibrils. Following MAGP2 secretion, PC cleavage occurs at the RLRR consensus site near the MAGP2 carboxyl‐terminus (CT). Since PC cleavage of Fbn‐1 is required for microfibril incorporation, we investigated the role PC cleavage plays in the localization of MAGP2 on microfibrils using immunocytochemistry. Transient expression of wild‐type MAGP2 in mouse ovarian epithelial cells that produce abundant Fbn‐2 microfibrils resulted in weak, but detectable extracellular MAGP2 fibers. Abundant MAGP2 fibers were generated when only the CT half of MAGP2 was expressed, confirming that the matrix‐binding domain in the CT half of MAGP2 is responsible for fiber localization. Mutation of the CT half of MAGP2 to prevent PC cleavage showed a small, but significant, decrease in extracellular MAGP2 fibers, indicating that PC cleavage promotes MAGP2‐microfibril binding. Preliminary data suggest that MAGP2 may bind preferentially to Fbn‐2 fibers, and that soluble MAGP2 can bind to microfibrils. Understanding the normal maturation and function of MAGP2 may be relevant to both angiogenesis and ovarian carcinoma progression, since previous studies implicate MAGP2 in both processes.