A mechanism of platelet integrin αIIbβ3 outside-in signaling through a novel integrin αIIb subunit-filamin-actin linkage.

ABSTRACT: The communication of talin-activated integrin αIIbβ3 with the cytoskeleton (integrin outside-in signaling) is essential for platelet aggregation, wound healing, and hemostasis. Filamin, a large actin crosslinker and integrin binding partner critical for cell spreading and migration, is implicated as a key regulator of integrin outside-in signaling. However, the current dogma is that filamin, which stabilizes inactive αIIbβ3, is displaced from αIIbβ3 by talin to promote the integrin activation (inside-out signaling), and how filamin further functions remains unresolved. Here, we show that while associating with the inactive αIIbβ3, filamin also associates with the talin-bound active αIIbβ3 to mediate platelet spreading. Fluorescence resonance energy transfer-based analysis reveals that whil

SUBMITTER: Liu J 

PROVIDER: S-EPMC10356577 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature