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- Title
Structural and functional analysis of LIM domain-dependent recruitment of paxillin to αvβ3 integrin-positive focal adhesions.
- Authors
Ripamonti, Marta; Liaudet, Nicolas; Azizi, Latifeh; Bouvard, Daniel; Hytönen, Vesa P.; Wehrle-Haller, Bernhard
- Abstract
The LIM domain-dependent localization of the adapter protein paxillin to β3 integrin-positive focal adhesions (FAs) is not mechanistically understood. Here, by combining molecular biology, photoactivation and FA-isolation experiments, we demonstrate specific contributions of each LIM domain of paxillin and reveal multiple paxillin interactions in adhesion-complexes. Mutation of β3 integrin at a putative paxillin binding site (β3VE/YA) leads to rapidly inward-sliding FAs, correlating with actin retrograde flow and enhanced paxillin dissociation kinetics. Induced mechanical coupling of paxillin to β3VE/YA integrin arrests the FA-sliding, thereby disclosing an essential structural function of paxillin for the maturation of β3 integrin/talin clusters. Moreover, bimolecular fluorescence complementation unveils the spatial orientation of the paxillin LIM-array, juxtaposing the positive LIM4 to the plasma membrane and the β3 integrin-tail, while in vitro binding assays point to LIM1 and/or LIM2 interaction with talin-head domain. These data provide structural insights into the molecular organization of β3 integrin-FAs. Ripamonti et al. provide mechanistic insight into the contribution of individual Paxillin LIM domains in targeting and maintaining the structural integrity of focal adhesions (FAs). They show that mechanical coupling of paxillin in the FA to the plasma membrane or integrin is important for FA stability and integrin-talin linkage.
- Subjects
FUNCTIONAL analysis; STRUCTURAL analysis (Science); PAXILLIN; TALINS (Proteins); INTEGRINS
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-01886-9