Fibulins and Elasticity
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Extracellular elastic fibers provide elasticity and resilience to tissues and contribute towards the processes of organ remodeling. The formation of elastic fibers requires the assembly and crosslinking of tropoelastin monomers, and organization of the resulting insoluble elastin matrix into functional fibers. Disruption of this process results in a broad spectrum of abnormalities, ranging from vascular and ocular defects to skeletal and skin disorders. However, the molecules and mechanisms involved in elastogenesis are not well understood. Fibulins, a relatively new extracellular matrix protein family, are abundantly expressed in elastic fiber-rich tissues. Mutations in various fibulin family members have been found in a number of heritable diseases including macular degeneration and cutis laxa. Through gene targeting in mice, we and others have found that deletion of selected fibulins causes elastinopathy. Some are more severe than others and result in perinatal lethality. From these results a model for how fibulins are involved in the assembly of elastic fibers can be derived.