In vivo regulation of integrin turnover by outside-in activation

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Abstract

The development of three-dimensional tissue architecture requires precise control over the attachment of cells to the extracellular matrix (ECM). Integrins, the main ECM-binding receptors in animals, are regulated in multiple ways to modulate cell-ECM adhesion. One example is the conformational activation of integrins by extracellular signals ('outside-in activation') or by intracellular signals ('inside-out activation'), whereas another is the modulation of integrin turnover. We demonstrate that outside-in activation regulates integrin turnover to stabilize tissue architecture in vivo. Treating Drosophila embryos with Mg2+ and Mn2+, known to induce outside-in activation, resulted in decreased integrin turnover. Mathematical modeling combined with mutational analysis provides mechanistic insight into the stabilization of integrins at the membrane. We show that as tissues mature, outside-in activation is crucial for regulating the stabilization of integrin-mediated adhesions. This data identifies a new in vivo role for outside-in activation and sheds light on the key transition between tissue morphogenesis and maintenance.

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López-Ceballos, P., DonajíHerrera-Reyes, A., Coombs, D., & Tanentzapf, G. (2016). In vivo regulation of integrin turnover by outside-in activation. Journal of Cell Science, 129(15), 2912–2924. https://doi.org/10.1242/jcs.190256

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