In vivo regulation of integrin turnover by outside-in activation

• Published in: Journal of cell science Vol. 129; no. 15; pp. 2912 - 2924
• Main Authors: López-Ceballos, Pablo, Herrera-Reyes, Alejandra Donají, Coombs, Daniel, Tanentzapf, Guy
• Format: Journal Article
• Language: English
• Published: England 01-08-2016
• Subjects: Animals; Cations, Divalent - pharmacology; Cell Adhesion; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Extracellular Matrix - metabolism; Integrins - metabolism; Ligands; Mutant Proteins - metabolism; Point Mutation - genetics; Telomere-Binding Proteins - metabolism; Activation; Mathematical modeling; Integrin; Drosophila; ECM; Turnover
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.190256

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 Mg(2+) and Mn(2+), 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.