Université Paris cité, CEA, INSERM, Institut de Recherche Saint Louis, UMR976 HIPI, CytoMorpho Lab, Avenue Claude Vellefaux, 75010 Paris, France.
Université Grenoble-Alpes, CEA, CNRS, INRA, Interdisciplinary Research Institute of Grenoble, UMR5168-LPCV, CytoMorpho Lab, Avenue des Martyrs, 38054 Grenoble, France.
J Cell Sci. 2023 Nov 15;136(22). doi: 10.1242/jcs.261667. Epub 2023 Nov 23.
The crosstalk between the actin network and microtubules is essential for cell polarity. It orchestrates microtubule organization within the cell, driven by the asymmetry of actin architecture along the cell periphery. The physical intertwining of these networks regulates spatial organization and force distribution in the microtubule network. Although their biochemical interactions are becoming clearer, the mechanical aspects remain less understood. To explore this mechanical interplay, we developed an in vitro reconstitution assay to investigate how dynamic microtubules interact with various actin filament structures. Our findings revealed that microtubules can align and move along linear actin filament bundles through polymerization force. However, they are unable to pass through when encountering dense branched actin meshworks, similar to those present in the lamellipodium along the periphery of the cell. Interestingly, immobilizing microtubules through crosslinking with actin or other means allow the buildup of pressure, enabling them to breach these dense actin barriers. This mechanism offers insights into microtubule progression towards the cell periphery, with them overcoming obstacles within the denser parts of the actin network and ultimately contributing to cell polarity establishment.
肌动蛋白网络和微管之间的串扰对于细胞极性至关重要。它通过细胞边缘沿肌动蛋白结构的不对称性来协调细胞内的微管组织。这些网络的物理交织调节微管网络中的空间组织和力分布。尽管它们的生化相互作用变得更加清晰,但机械方面的理解仍然较少。为了探索这种机械相互作用,我们开发了一种体外重组测定法来研究动态微管如何与各种肌动蛋白丝结构相互作用。我们的研究结果表明,微管可以通过聚合力沿着线性肌动蛋白丝束排列并移动。然而,当遇到密集的分支肌动蛋白网格时,它们无法通过,类似于细胞边缘的片状伪足中存在的网格。有趣的是,通过与肌动蛋白或其他方式交联固定微管会导致压力积聚,从而使它们能够突破这些密集的肌动蛋白障碍。这种机制为微管向细胞边缘的推进提供了深入了解,使它们克服了肌动蛋白网络中较密集部分的障碍,并最终有助于细胞极性的建立。