1061, Hirai et al. report that youthful elastic fibers are assembled by an extracellular matrix protein that slips away with age.
Mice that lack this matrix protein, called fibulin-5, have loose, wrinkled skin, vascular abnormalities, and emphysema, all of which are thought to be due to their disorganized and fragmented elastic fibers.
Elastic fibers are composed of an inner core of cross-linked elastin surrounded by a microfibril envelope. Hirai et al. now show that fibulin-5 generates elastic fibers by promoting aggregation of the elastin precursor, called tropoelastin, its deposition onto microfibrils, and its cross-linking into mature elastin.
A naturally occurring truncated version of fibulin-5 that did not associate with microfibrils was unable to promote elastic fiber assembly. This truncated version accumulated with age, while the full-length, microfibril-associating version diminished.
The shorter version of fibulin-5 is formed by the action of a serine protease, which cleaves off the NH2-terminal region of the full-length protein. The team is currently investigating the identity of this protease and trying to determine why it promotes more cleavage with age.