Tmod1 and CP49 synergize to control the fiber cell geometry, transparency, and mechanical stiffness of the mouse lens.
Tmod1 and CP49 synergize to control the fiber cell geometry, transparency, and mechanical stiffness of the mouse lens.
复制标题
DOI：
10.1371/journal.pone.0048734
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fowler VM
中科院分区：
文献类型：
--
作者：
Gokhin DS;Nowak RB;Kim NE;Arnett EE;Chen AC;Sah RL;Clark JI;Fowler VM
哺乳动物晶状体纤维细胞的组织、透明度和生物力学特性的基础来自两个专门的细胞骨架系统：血影蛋白-肌动蛋白膜骨架和珠状细丝细胞骨架。血影蛋白-肌动蛋白膜骨架主要由α2β2-血影蛋白链组成，它们相互连接短的、原肌球蛋白包裹的肌动蛋白细丝，由原肌球蛋白1(Tmod1)点端封顶稳定，在没有Tmod1的情况下结构破坏。珠状细丝细胞骨架由中间细丝蛋白CP49和细丝蛋白组成，它们需要CP49进行组装，有助于晶状体透明和生物力学。为了评估这些细胞骨架网络的同时生理作用，并揭示它们之间潜在的功能协同作用，我们对缺乏Tmod1和/或CP49的小鼠的晶状体进行了一系列结构和生理分析，以分析纤维细胞紊乱、光散射和压缩生物力学特性。结果表明，Tmod1和/或CP49的缺失增加了晶状体纤维细胞的无序和光散射，同时削弱了压缩负荷，与任一单一突变体相比，双突变体表现出不同的表型。此外，Tmod1与CP49和细丝蛋白处于蛋白质复合体中，这表明血影蛋白-肌动蛋白网络和珠状细丝细胞骨架在生物化学上是相连的。这些实验表明，光影蛋白-肌动蛋白膜骨架和珠状细丝细胞骨架建立了一种新的功能协同，对调节晶状体纤维细胞的几何形状、透明度和机械硬度至关重要。
The basis for mammalian lens fiber cell organization, transparency, and biomechanical properties has contributions from two specialized cytoskeletal systems: the spectrin-actin membrane skeleton and beaded filament cytoskeleton. The spectrin-actin membrane skeleton predominantly consists of α2β2-spectrin strands interconnecting short, tropomyosin-coated actin filaments, which are stabilized by pointed-end capping by tropomodulin 1 (Tmod1) and structurally disrupted in the absence of Tmod1. The beaded filament cytoskeleton consists of the intermediate filament proteins CP49 and filensin, which require CP49 for assembly and contribute to lens transparency and biomechanics. To assess the simultaneous physiological contributions of these cytoskeletal networks and uncover potential functional synergy between them, we subjected lenses from mice lacking Tmod1, CP49, or both to a battery of structural and physiological assays to analyze fiber cell disorder, light scattering, and compressive biomechanical properties. Findings show that deletion of Tmod1 and/or CP49 increases lens fiber cell disorder and light scattering while impairing compressive load-bearing, with the double mutant exhibiting a distinct phenotype compared to either single mutant. Moreover, Tmod1 is in a protein complex with CP49 and filensin, indicating that the spectrin-actin network and beaded filament cytoskeleton are biochemically linked. These experiments reveal that the spectrin-actin membrane skeleton and beaded filament cytoskeleton establish a novel functional synergy critical for regulating lens fiber cell geometry, transparency, and mechanical stiffness.
登录
查看更多内容
DOI：
10.1083/jcb.201001125
发表时间：
2010-04-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gokhin DS;Lewis RA;McKeown CR;Nowak RB;Kim NE;Littlefield RS;Lieber RL;Fowler VM
通讯作者：
Fowler VM
影响因子：
4.4
作者：
Blankenship, Tom;Bradshaw, Linsey;FitzGerald, Paul
通讯作者：
FitzGerald, Paul
影响因子：
2.4
作者：
Klein, Travis J.;Chaudhry, Manu;Sah, Robert L.
通讯作者：
Sah, Robert L.
DOI：
10.1073/pnas.0808987105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Cooper, Margaret A.;Son, Alexander I.;Zhou, Renping
通讯作者：
Zhou, Renping
影响因子：
2.4
作者：
Chen, AC;Bae, WC;Sah, RL
通讯作者：
Sah, RL