Cytoskeleton-mediated forces regulate the assembly and function of integrin adhesions; however, the underlying mechanisms remain unclear. The tripartite IPP complex, comprising ILK, Parvin, and PINCH, mediates the integrin-actin link at Drosophila embryo muscle attachment sites (MASs). Here, we demonstrate a developmentally earlier function for the IPP complex: to reinforce integrin-extracellular matrix (ECM) adhesion in response to tension. In IPP-complex mutants, the integrin-ECM linkage at MASs breaks in response to intense muscle contractility. Mechanistically, the IPP complex is required to relay force-elicited signals that decelerate integrin turnover at the plasma membrane so that the integrin immobile fraction is adequate to withstand tension. Epistasis analysis shows that alleviation of muscle contractility, downregulation of endocytosis, and enhanced integrin binding to the ECM are sufficient to restore integrin-ECM adhesion and maintain integrin-adhesome organization in IPP-complex mutants. Our findings reveal a role for the IPP complex as an essential mechanosensitive regulatory switch of integrin turnover in vivo.

In the originally published version of this article, a modified version of the pre-existing easyFRAP software tool (Rapsomaniki et al., 2012) based on the mathematical modeling described in Pines et al. (2012) was used for the analysis of bPS-GFP FRAP data. It has come to our attention that the script used for this adapted version was not published prior to this publication. Therefore, we would like to add Maria Anna Rapsomaniki and Zoi Lygerou, who provided the script, as authors of this paper. The corrected author list appears here, as well as in the current, updated version of the paper available online. In addition, the Supplemental Experimental Procedures section has been updated to include a weblink directing readers to the modified easyFRAP version available for download (http://ccl.med.upatras.gr/index.php?id=easyfrap-betapsintegrin). Lastly, Maria Anna Rapsomaniki, who is now included as a coauthor, was previously mentioned in the Acknowledgments section, and that text has been removed in the updated version of the paper. The authors regret the omission and any confusion it may have caused.