β-arrestin 1 and integrin-linked kinase interact in epidermal keratinocytes and regulate cell motility.

Arrestins and integrin-linked kinase (ILK) are important scaffold proteins that regulate myriad cell functions in metazoans. β-arrestins, first identified as critical components in G-protein-coupled receptor (GPCR) signaling pathways, participate in inflammatory, immunomodulatory and tissue repair processes in GPCR-dependent and -independent manners. ILK is a central mediator of signaling cascades elicited by activation of integrins, regulating cell motility, proliferation, and mechanotransduction. In the epidermis, ILK is essential for maintenance of barrier function, hair follicle development, melanocyte colonization and regeneration after injury. In this tissue, β-arrestin 2 mitigates inflammatory processes and development of allergic dermatitis, which also is associated with loss of epidermal barrier function. However, the functional role of β-arrestin 1 in epidermal cells is poorly understood. We now report that β-arrestin 1 directly binds ILK, forming hitherto unidentified protein complexes in epidermal keratinocytes. In the absence of exogenous GPCR ligand stimulation, β-arrestin 1 and ILK are found throughout the cytoplasm in epidermal keratinocytes, and also co-localize to plasma membrane regions associated with cell protrusions. Inactivation of the genes that encode both β-arrestin 1 and 2 attenuates forward cell migration, whereas expression of ILK together with β-arrestin 1 restores cell motility. The cooperative effect of ILK and β-arrestin 1 in promoting directional cell migration may have important implications for epidermal regeneration and reestablishment of barrier function after injury.