αvβ8 integrin adhesion and signaling pathways in development, physiology and disease

Cells must interpret a complex milieu of extracellular cues to modulate intracellular signaling events linked to proliferation, differentiation, migration and other cellular processes. Integrins are heterodimeric transmembrane proteins that link the extracellular matrix (ECM) to the cytoskeleton and control intracellular signaling events. A great deal is known about the structural and functional properties for most integrins; however, the adhesion and signaling pathways controlled by αvβ8 integrin, which was discovered nearly 30 years ago, have only recently been characterized. αvβ8 integrin is a receptor for ECM-bound forms of latent transforming growth factor β (TGFβ) proteins and promotes the activation of TGFβ signaling pathways. Studies of the brain, lung and immune system reveal that the αvβ8 integrin-TGFβ axis mediates cell-cell contact and communication within complex multicellular structures. Perturbing components of this axis results in aberrant cell-cell adhesion and signaling leading to the initiation of various pathologies, including neurodegeneration, fibrosis and cancer. As discussed in this Review, understanding the functions for αvβ8 integrin, its ECM ligands and intracellular effector proteins is not only an important topic in cell biology, but may lead to new therapeutic strategies to treat human pathologies related to integrin dysfunction.