Faculty of Biological and Environmental Sciences, University of Helsinki, FI-00014, Helsinki, Finland.
Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Cell Mol Life Sci. 2024 Jun 4;81(1):248. doi: 10.1007/s00018-024-05294-0.
Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1 plays a central role in orchestrating the maturation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process.
收缩性肌动球蛋白束在多种生理过程中发挥着关键作用，包括细胞迁移、形态发生和肌肉收缩。肌球蛋白 II 丝的精确排列和融合涉及肌动球蛋白束的复杂组装，但这些过程中涉及的潜在机制和因素仍不清楚。我们的研究表明，LUZP1 在协调厚肌动球蛋白束的成熟中起着核心作用。LUZP1 的缺失导致细胞形态发生、迁移和对环境施加力的能力异常。重要的是，LUZP1 的敲除导致肌球蛋白 II 丝的串联和持续关联出现严重缺陷，严重损害了肌球蛋白 II 堆积的组装。在 LUZP1 敲除细胞中这些过程的破坏为厚腹侧应激纤维的缺陷组装以及相关的细胞收缩性异常提供了机制见解。总的来说，这些结果极大地促进了我们对肌动球蛋白束形成中涉及的分子机制的理解，并强调了 LUZP1 在这个过程中的重要作用。
