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从应力纤维到粘着斑:肌动蛋白交联蛋白在力传递中的作用

From stress fiber to focal adhesion: a role of actin crosslinkers in force transmission.

作者信息

Katsuta Hiroki, Sokabe Masahiro, Hirata Hiroaki

机构信息

Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

Human Information Systems Laboratories, Kanazawa Institute of Technology, Hakusan, Japan.

出版信息

Front Cell Dev Biol. 2024 Aug 13;12:1444827. doi: 10.3389/fcell.2024.1444827. eCollection 2024.

Abstract

The contractile apparatus, stress fiber (SF), is connected to the cell adhesion machinery, focal adhesion (FA), at the termini of SF. The SF-FA complex is essential for various mechanical activities of cells, including cell adhesion to the extracellular matrix (ECM), ECM rigidity sensing, and cell migration. This mini-review highlights the importance of SF mechanics in these cellular activities. Actin-crosslinking proteins solidify SFs by attenuating myosin-driven flows of actin and myosin filaments within the SF. In the solidified SFs, viscous slippage between actin filaments in SFs and between the filaments and the surrounding cytosol is reduced, leading to efficient transmission of myosin-generated contractile force along the SFs. Hence, SF solidification via actin crosslinking ensures exertion of a large force to FAs, enabling FA maturation, ECM rigidity sensing and cell migration. We further discuss intracellular mechanisms for tuning crosslinker-modulated SF mechanics and the potential relationship between the aberrance of SF mechanics and pathology including cancer.

摘要

收缩装置,即应力纤维(SF),在SF的末端与细胞黏附机制,即黏着斑(FA)相连。SF-FA复合体对于细胞的各种机械活动至关重要,包括细胞与细胞外基质(ECM)的黏附、ECM硬度感知以及细胞迁移。这篇小型综述强调了SF力学在这些细胞活动中的重要性。肌动蛋白交联蛋白通过减弱肌球蛋白驱动的SF内肌动蛋白丝和肌球蛋白丝的流动来固化SF。在固化的SF中,SF内肌动蛋白丝之间以及肌动蛋白丝与周围细胞质之间的粘性滑动减少,从而导致肌球蛋白产生的收缩力沿SF有效传递。因此,通过肌动蛋白交联实现的SF固化可确保向FA施加大力,从而实现FA成熟、ECM硬度感知和细胞迁移。我们进一步讨论了调节交联剂调节的SF力学的细胞内机制,以及SF力学异常与包括癌症在内的病理学之间的潜在关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b03/11347286/84dc1907c9b2/fcell-12-1444827-g001.jpg

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