Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
Name
elife-72588-v2.pdf
Description
Published version
Size
7.33 MB
Format
Adobe PDF
Checksum (MD5)
27892102f882835ba1068c3370cf0dac
Author(s)
Case, Lindsay B
De Pasquale, Milagros
Henry, Lisa
Rosen, Michael K
Date Issued
2022
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Case, Lindsay B, De Pasquale, Milagros, Henry, Lisa and Rosen, Michael K. 2022. "Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation." eLife, 11.
Version
Final published version
Abstract
Integrin adhesion complexes (IACs) are integrin-based plasma-membrane-associated compartments where cells sense environmental cues. The physical mechanisms and molecular interactions that mediate initial IAC formation are unclear. We found that both p130Cas (‘Cas’) and Focal adhesion kinase (‘FAK’) undergo liquid-liquid phase separation in vitro under physiologic conditions. Cas- and FAK- driven phase separation is sufficient to reconstitute kindlin-dependent integrin clustering in vitro with recombinant mammalian proteins. In vitro condensates and IACs in mouse embryonic fibroblasts (MEFs) exhibit similar sensitivities to environmental perturbations including changes in temperature and pH. Furthermore, mutations that inhibit or enhance phase separation in vitro reduce or increase the number of IACs in MEFs, respectively. Finally, we find that the Cas and FAK pathways act synergistically to promote phase separation, integrin clustering, IAC formation and partitioning of key components in vitro and in cells. We propose that Cas- and FAK-driven phase separation provides an intracellular trigger for integrin clustering and nascent IAC formation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.7554/ELIFE.72588
