Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes.
Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes.
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DOI：
10.1083/jcb.201510036
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发表时间：
2016-06-06
期刊：
影响因子：
--
通讯作者：
Destaing O
中科院分区：
文献类型：
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作者：
Petropoulos C;Oddou C;Emadali A;Hiriart-Bryant E;Boyault C;Faurobert E;Vande Pol S;Kim-Kaneyama JR;Kraut A;Coute Y;Block M;Albiges-Rizo C;Destaing O
所有paxillin家族成员在侵润体的机械传感和粘附中的确切功能尚不清楚。Petropoulos等人表明，paxillin和Hic-5的冗余和特异性活性可以将侵入体中的原始粘附和ECM降解结合起来。内溶体是一种动作粘附结构，既能结合细胞外基质（ECM），又能消化它。Paxillin家族成员- Paxillin， Hic-5和leupaxin -与粘附位点的机械传感和周转有关，但每个Paxillin家族蛋白对侵入体活性的贡献尚不清楚。我们使用遗传方法来证明paxillin和Hic-5在侵入体形成中具有冗余和独特的功能。paxillin样活性的基本功能是基于LD基序和LIM结构域的协同活性，它们分别支持侵入体组装和形态。然而，paxillin优先调节侵入体组装，而Hic-5调节ECM降解和行为粘附功能之间的耦合。质谱分析揭示了paxillin和Hic-5特异性的重要新伙伴：paxillin通过janus kinase 1 （JAK1）调节动作粘附机制，而Hic-5通过IQGAP1控制ECM降解。将paxillin和Hic-5的冗余性和特异性整合到一个功能复合物中，可以深入了解侵入体中行为粘附和ecm降解机制之间的耦合。
The exact functions of all paxillin family members in mechanosensing and adhesion at invadosomes are unclear. Petropoulos et al. show that redundant and specific activities of paxillin and Hic-5 can couple original adhesion and ECM degradation in invadosomes. Invadosomes are acto-adhesive structures able to both bind the extracellular matrix (ECM) and digest it. Paxillin family members—paxillin, Hic-5, and leupaxin—are implicated in mechanosensing and turnover of adhesion sites, but the contribution of each paxillin family protein to invadosome activities is unclear. We use genetic approaches to show that paxillin and Hic-5 have both redundant and distinctive functions in invadosome formation. The essential function of paxillin-like activity is based on the coordinated activity of LD motifs and LIM domains, which support invadosome assembly and morphology, respectively. However, paxillin preferentially regulates invadosome assembly, whereas Hic-5 regulates the coupling between ECM degradation and acto-adhesive functions. Mass spectrometry analysis revealed new partners that are important for paxillin and Hic-5 specificities: paxillin regulates the acto-adhesive machinery through janus kinase 1 (JAK1), whereas Hic-5 controls ECM degradation via IQGAP1. Integrating the redundancy and specificities of paxillin and Hic-5 in a functional complex provides insights into the coupling between the acto-adhesive and ECM-degradative machineries in invadosomes.