CEA, CNRS, INRA, Biosciences & Biotechnology Institute of Grenoble, UMR5168, CytoMorpho Lab, Univ. Grenoble-Alpes, Grenoble, France.
INSERM, U932 Immunité et Cancer, Institut Curie, PSL Research University, Paris, France.
EMBO J. 2019 Jun 3;38(11). doi: 10.15252/embj.201899630. Epub 2019 Mar 22.
The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here, we show that increasing densities of actin filaments at the centrosome of lymphocytes are correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in disassembly of centrosomal actin and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed reconstitution assays based on (i) purified centrosomes and (ii) on the co-micropatterning of microtubule seeds and actin filaments. These two assays demonstrated that actin filaments constitute a physical barrier blocking elongation of nascent microtubules. Finally, we showed that cell adhesion and cell spreading lead to lower densities of centrosomal actin, thus resulting in higher microtubule growth. We therefore propose a novel mechanism, by which the number of centrosomal microtubules is regulated by cell adhesion and actin-network architecture.
中心体是主要的微管组织中心。它还组织了局部的肌动蛋白丝网络。然而,中心体处的肌动蛋白网络的确切功能还不是很清楚。在这里,我们发现淋巴细胞中心体处肌动蛋白丝密度的增加与微管数量的减少有关。此外,淋巴细胞的激活导致中心体处的肌动蛋白解聚和微管数量的增加。为了进一步研究中心体处肌动蛋白和微管之间的直接相互作用,我们进行了基于(i)纯化的中心体和(ii)微管种子和肌动蛋白丝共微图案化的重建实验。这两个实验表明,肌动蛋白丝构成了一个物理屏障,阻止了新生微管的延伸。最后,我们表明细胞黏附和细胞铺展导致中心体处的肌动蛋白密度降低,从而导致微管生长增加。因此,我们提出了一个新的机制,即细胞黏附和肌动蛋白网络结构调节中心体处的微管数量。