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整合素通过控制基底肌动蛋白网络的结构和力学特性来调节上皮细胞的形状。

Integrins regulate epithelial cell shape by controlling the architecture and mechanical properties of basal actomyosin networks.

机构信息

Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide/CSIC/JA, Carretera de Utrera,Sevilla, Spain.

School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.

出版信息

PLoS Genet. 2020 Jun 1;16(6):e1008717. doi: 10.1371/journal.pgen.1008717. eCollection 2020 Jun.

Abstract

Forces generated by the actomyosin cytoskeleton are key contributors to many morphogenetic processes. The actomyosin cytoskeleton organises in different types of networks depending on intracellular signals and on cell-cell and cell-extracellular matrix (ECM) interactions. However, actomyosin networks are not static and transitions between them have been proposed to drive morphogenesis. Still, little is known about the mechanisms that regulate the dynamics of actomyosin networks during morphogenesis. This work uses the Drosophila follicular epithelium, real-time imaging, laser ablation and quantitative analysis to study the role of integrins on the regulation of basal actomyosin networks organisation and dynamics and the potential contribution of this role to cell shape. We find that elimination of integrins from follicle cells impairs F-actin recruitment to basal medial actomyosin stress fibers. The available F-actin redistributes to the so-called whip-like structures, present at tricellular junctions, and into a new type of actin-rich protrusions that emanate from the basal cortex and project towards the medial region. These F-actin protrusions are dynamic and changes in total protrusion area correlate with periodic cycles of basal myosin accumulation and constriction pulses of the cell membrane. Finally, we find that follicle cells lacking integrin function show increased membrane tension and reduced basal surface. Furthermore, the actin-rich protrusions are responsible for these phenotypes as their elimination in integrin mutant follicle cells rescues both tension and basal surface defects. We thus propose that the role of integrins as regulators of stress fibers plays a key role on controlling epithelial cell shape, as integrin disruption promotes reorganisation into other types of actomyosin networks, in a manner that interferes with proper expansion of epithelial basal surfaces.

摘要

肌动球蛋白细胞骨架产生的力是许多形态发生过程的关键贡献者。肌动球蛋白细胞骨架根据细胞内信号以及细胞-细胞和细胞-细胞外基质(ECM)相互作用,组织成不同类型的网络。然而,肌动球蛋白网络不是静态的,并且已经提出它们之间的转变可以驱动形态发生。尽管如此,关于调节形态发生过程中肌动球蛋白网络动态的机制知之甚少。这项工作使用果蝇滤泡上皮细胞、实时成像、激光消融和定量分析来研究整合素在调节基底肌动球蛋白网络组织和动力学中的作用,以及这种作用对细胞形状的潜在贡献。我们发现,从滤泡细胞中消除整合素会损害 F-肌动蛋白募集到基底中侧肌动球蛋白应激纤维。可用的 F-肌动蛋白重新分配到所谓的鞭状结构中,存在于三细胞连接处,并进入一种新的富含肌动蛋白的突起,从基底皮质发出并伸向中侧区域。这些 F-肌动蛋白突起是动态的,总突起面积的变化与基底肌球蛋白积累的周期性循环和细胞膜的收缩脉冲相关。最后,我们发现缺乏整合素功能的滤泡细胞表现出增加的膜张力和减少的基底表面。此外,富含肌动蛋白的突起是这些表型的原因,因为在整合素突变滤泡细胞中消除这些突起可以挽救张力和基底表面缺陷。因此,我们提出整合素作为应激纤维调节剂的作用对于控制上皮细胞形状起着关键作用,因为整合素的破坏促进了其他类型的肌动球蛋白网络的重组,以干扰上皮基底表面的适当扩张。

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