期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 15, 页码 2912-2924出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.190256
关键词
Drosophila; Integrin; Turnover; Activation; Mathematical modeling; ECM
类别
资金
- Canadian Institutes of Health Research (CIHR) [MOP-285391]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [356502, RGPIN-2015-04611]
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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