Nejedla Michaela, Sadi Sara, Sulimenko Vadym, de Almeida Francisca Nunes, Blom Hans, Draber Pavel, Aspenström Pontus, Karlsson Roger
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.
Institute of Molecular Genetics, ASCR, 142 20 Prague 4, Czech Republic.
Mol Biol Cell. 2016 Aug 1;27(15):2381-93. doi: 10.1091/mbc.E15-11-0799. Epub 2016 Jun 15.
Profilin controls actin nucleation and assembly processes in eukaryotic cells. Actin nucleation and elongation promoting factors (NEPFs) such as Ena/VASP, formins, and WASP-family proteins recruit profilin:actin for filament formation. Some of these are found to be microtubule associated, making actin polymerization from microtubule-associated platforms possible. Microtubules are implicated in focal adhesion turnover, cell polarity establishment, and migration, illustrating the coupling between actin and microtubule systems. Here we demonstrate that profilin is functionally linked to microtubules with formins and point to formins as major mediators of this association. To reach this conclusion, we combined different fluorescence microscopy techniques, including superresolution microscopy, with siRNA modulation of profilin expression and drug treatments to interfere with actin dynamics. Our studies show that profilin dynamically associates with microtubules and this fraction of profilin contributes to balance actin assembly during homeostatic cell growth and affects micro-tubule dynamics. Hence profilin functions as a regulator of microtubule (+)-end turnover in addition to being an actin control element.
丝切蛋白控制真核细胞中的肌动蛋白成核和组装过程。诸如Ena/VASP、formin和WASP家族蛋白等肌动蛋白成核和延伸促进因子(NEPFs)招募丝切蛋白:肌动蛋白以形成细丝。其中一些被发现与微管相关,使得从微管相关平台进行肌动蛋白聚合成为可能。微管参与粘着斑周转、细胞极性建立和迁移,说明了肌动蛋白和微管系统之间的耦合。在这里,我们证明丝切蛋白在功能上通过formin与微管相连,并指出formin是这种关联的主要介质。为了得出这一结论,我们将包括超分辨率显微镜在内的不同荧光显微镜技术与丝切蛋白表达的siRNA调节和药物处理相结合,以干扰肌动蛋白动力学。我们的研究表明,丝切蛋白动态地与微管结合,并且这部分丝切蛋白有助于在稳态细胞生长过程中平衡肌动蛋白组装,并影响微管动力学。因此,丝切蛋白除了作为肌动蛋白控制元件外,还作为微管(+)端周转的调节剂发挥作用。