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细胞手性源于肌动蛋白细胞骨架的自组织。

Cellular chirality arising from the self-organization of the actin cytoskeleton.

机构信息

Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.

Faculty of Biology, Technion - Israel Institute of Technology, Haifa 32000, Israel.

出版信息

Nat Cell Biol. 2015 Apr;17(4):445-57. doi: 10.1038/ncb3137. Epub 2015 Mar 23.

Abstract

Cellular mechanisms underlying the development of left-right asymmetry in tissues and embryos remain obscure. Here, the development of a chiral pattern of actomyosin was revealed by studying actin cytoskeleton self-organization in cells with isotropic circular shape. A radially symmetrical system of actin bundles consisting of α-actinin-enriched radial fibres (RFs) and myosin-IIA-enriched transverse fibres (TFs) evolved spontaneously into the chiral system as a result of the unidirectional tilting of all RFs, which was accompanied by a tangential shift in the retrograde movement of TFs. We showed that myosin-IIA-dependent contractile stresses within TFs drive their movement along RFs, which grow centripetally in a formin-dependent fashion. The handedness of the chiral pattern was shown to be regulated by α-actinin-1. Computational modelling demonstrated that the dynamics of the RF-TF system can explain the pattern transition from radial to chiral. Thus, actin cytoskeleton self-organization provides built-in machinery that potentially allows cells to develop left-right asymmetry.

摘要

细胞内左右不对称性发育的机制仍不清楚。在这里,通过研究具有各向同性圆形形状的细胞中的肌动蛋白细胞骨架的自组织,揭示了肌动球蛋白的手性模式的发育。由于所有 RF 的单向倾斜,富含 α-辅肌动蛋白的放射状纤维 (RFs) 和富含肌球蛋白-IIA 的横向纤维 (TFs) 的放射状对称系统自发演变成手性系统,同时 TF 的逆行运动发生了切向移位。我们表明,TFs 内肌球蛋白-IIA 依赖性收缩力驱动它们沿着 RF 移动,而 RF 则以formin 依赖性方式向心生长。手性模式的手性由 α-辅肌动蛋白-1 调节。计算模型表明,RF-TF 系统的动力学可以解释从放射状到手性的模式转变。因此,肌动蛋白细胞骨架的自组织提供了内置机制,使细胞有可能发育出左右不对称性。

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