Many tissues require high elasticity for their function. To form elastic fibres, tropoelastin monomers are assembled and crosslinked into an insoluble extracellular matrix, which is organized into functional fibres. But the molecular mechanisms that control the supramolecular organization of elastic fibres have so far been a mystery. Two papers published in Nature now show that the integrin ligand fibulin-5 is essential for this process.

The two groups independently created fibulin-5 knock-out mouse strains and found that the mice, although viable, had defects related to tissue elasticity, which worsened with age. Skin, lungs and large arteries — tissues that are normally highly elastic — were most affected. The mice had loose skin, severe emphysema (that resulted from expanded lungs with dilated alveoli), and a tortuous and elongated aorta. Microscopic inspection of the affected tissues indicated that, although elastic fibres were present, they were short and disorganized.

These defects pointed to the involvement of fibulin-5 in the organization of elastic fibres. Indeed, Olson and colleagues found that fibulin-5 interacts with elastin in a calcium-dependent manner in a solid-phase binding assay, and Chien and colleagues showed that it is recruited to elastic fibres produced by mouse-skin fibroblasts grown in culture.

Chien and colleagues also analysed the interaction between fibulin-5 and integrins, and found that fibulin-5 can promote cell attachment in cells that express αvβ3, αvβ5 or α9β1.

Both groups conclude that fibulin-5 probably links elastic fibres to the cell surface and thereby somehow organizes elastin polymers into functional elastic fibres. An added bonus of these studies is that the mutant mice might be a good model for studying ageing, as they have some of its more striking features — sagging skin, breathing difficulties and high-pulse pressure.