Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation

Lindsay B. Case, Milagros De Pasquale, Lisa Henry, Michael K. Rosen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere72588
JournaleLife
Volume11
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint

Dive into the research topics of 'Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation'. Together they form a unique fingerprint.

Cite this