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Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
by
Case, Lindsay B
, Henry, Lisa
, De Pasquale, Milagros
, Rosen, Michael K
in
Adhesion
/ Analysis
/ Animals
/ Biochemistry and Chemical Biology
/ Cell Adhesion
/ Cell Adhesion Molecules - metabolism
/ Cell Biology
/ Cell cycle
/ Cell Line
/ Embryo fibroblasts
/ FAK
/ Fibroblasts - physiology
/ focal adhesion
/ Focal adhesion kinase
/ Focal Adhesion Protein-Tyrosine Kinases - genetics
/ Focal Adhesion Protein-Tyrosine Kinases - metabolism
/ integrin adhesion complex
/ Integrins
/ Integrins - genetics
/ Integrins - metabolism
/ Kinases
/ Ligands
/ Mice
/ Microscopy
/ Mutation
/ p130Cas
/ phase separation
/ Phosphorylation
/ Proteins
/ Sf9 Cells
/ Signal Transduction
2022
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Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
by
Case, Lindsay B
, Henry, Lisa
, De Pasquale, Milagros
, Rosen, Michael K
in
Adhesion
/ Analysis
/ Animals
/ Biochemistry and Chemical Biology
/ Cell Adhesion
/ Cell Adhesion Molecules - metabolism
/ Cell Biology
/ Cell cycle
/ Cell Line
/ Embryo fibroblasts
/ FAK
/ Fibroblasts - physiology
/ focal adhesion
/ Focal adhesion kinase
/ Focal Adhesion Protein-Tyrosine Kinases - genetics
/ Focal Adhesion Protein-Tyrosine Kinases - metabolism
/ integrin adhesion complex
/ Integrins
/ Integrins - genetics
/ Integrins - metabolism
/ Kinases
/ Ligands
/ Mice
/ Microscopy
/ Mutation
/ p130Cas
/ phase separation
/ Phosphorylation
/ Proteins
/ Sf9 Cells
/ Signal Transduction
2022
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Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
by
Case, Lindsay B
, Henry, Lisa
, De Pasquale, Milagros
, Rosen, Michael K
in
Adhesion
/ Analysis
/ Animals
/ Biochemistry and Chemical Biology
/ Cell Adhesion
/ Cell Adhesion Molecules - metabolism
/ Cell Biology
/ Cell cycle
/ Cell Line
/ Embryo fibroblasts
/ FAK
/ Fibroblasts - physiology
/ focal adhesion
/ Focal adhesion kinase
/ Focal Adhesion Protein-Tyrosine Kinases - genetics
/ Focal Adhesion Protein-Tyrosine Kinases - metabolism
/ integrin adhesion complex
/ Integrins
/ Integrins - genetics
/ Integrins - metabolism
/ Kinases
/ Ligands
/ Mice
/ Microscopy
/ Mutation
/ p130Cas
/ phase separation
/ Phosphorylation
/ Proteins
/ Sf9 Cells
/ Signal Transduction
2022
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Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
Journal Article
Synergistic phase separation of two pathways promotes integrin clustering and nascent adhesion formation
2022
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Overview
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.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
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