In vivo regulation of integrin turnover by outside-in activation.
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.
Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Pablo
P
López-Ceballos
Department of Mathematics and Institute of Applied Mathematics, 1984 Mathematics Road, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z2.
Alejandra Donají
0000-0002-8666-040X
AD
Herrera-Reyes
Department of Mathematics and Institute of Applied Mathematics, 1984 Mathematics Road, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z2.
Daniel
D
Coombs
Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 tanentz@mail.ubc.ca.
Guy
0000-0002-2443-233X
G
Tanentzapf
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D050505:Mutant Proteins / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism
D002413:Cations, Divalent; D029721:Drosophila Proteins; D016023:Integrins; D008024:Ligands; D050505:Mutant Proteins; C000607855:RAP1 protein, Drosophila; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins
Activation; Drosophila; ECM; Integrin; Mathematical modeling; Turnover