PT  - JOURNAL ARTICLE
AU  - Yujie Li
AU  - Ting Zhang
AU  - Huadong Li
AU  - Haibin Yang
AU  - Ruihong Lin
AU  - Kang Sun
AU  - Lei Wang
AU  - Jing Zhang
AU  - Zhiyi Wei
AU  - Cong Yu
TI  - Kindlin2-mediated phase separation underlies integrin adhesion formation
AID  - 10.1101/2020.07.10.197400
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.10.197400
4099  - http://biorxiv.org/content/early/2020/07/10/2020.07.10.197400.short
4100  - http://biorxiv.org/content/early/2020/07/10/2020.07.10.197400.full
AB  - Formation of cell-extracellular matrix adhesion requires assembly of the transmembrane receptor integrins and their intracellular activators, kindlin and talin proteins in minutes. The mechanisms governing the rapid formation and dynamics of the adhesion remain enigmatic. Here, we reported that the dimerized-kindlin2 underwent phase separation with clustered-integrin in solution and on lipid bilayer. The kindlin2/integrin condensate can further enrich other components for the adhesion complex assembly. The full-length structure of kindlin2 was solved and revealed that the kindlin2 dimers can further pack with each other to form a higher oligomer. Disrupting the intermolecular interaction between the kindlin2 dimer inhibits the phase formation on 2D membrane in vitro and impaired the adhesion formation, integrin activation, and cell spreading in cultured cells. We also determined the full-length structure of kindlin2 in its monomeric conformation. Structural analysis and biochemical characterization indicate that the interdomain interaction control the monomer-dimer transition of kindlin2, providing a regulation mechanism of the kindlin2-mediated phase separation. Our findings not only provide a mechanistic explanation for the formation and dynamic regulation of the integrin-based adhesion, but also shed light on understanding of how the clustered receptors participate in assembly of the functional membrane domains via phase separation.Competing Interest StatementThe authors have declared no competing interest.