Journal
COMMUNICATIONS BIOLOGY
Volume 4, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-021-01886-9
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Funding
- Swiss National Science Foundation [31003A_166384, 310030_185261]
- Academy of Finland [331946]
- Swiss National Science Foundation (SNF) [31003A_166384, 310030_185261] Funding Source: Swiss National Science Foundation (SNF)
- Academy of Finland (AKA) [331946, 331946] Funding Source: Academy of Finland (AKA)
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The study provides insights into the molecular organization of beta 3 integrin-FAs, showing the specific contributions of individual Paxillin LIM domains in targeting and maintaining the structural integrity of focal adhesions (FAs). Ripamonti et al. demonstrate the importance of mechanical coupling of paxillin in the FA to the plasma membrane or integrin for FA stability and integrin-talin linkage.
The LIM domain-dependent localization of the adapter protein paxillin to beta 3 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 beta 3 integrin at a putative paxillin binding site (beta 3(VE/YA)) leads to rapidly inward-sliding FAs, correlating with actin retrograde flow and enhanced paxillin dissociation kinetics. Induced mechanical coupling of paxillin to beta 3(VE/YA) integrin arrests the FA-sliding, thereby disclosing an essential structural function of paxillin for the maturation of beta 3 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 beta 3 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 beta 3 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.
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