The Load-Bearing Mechanosome Revisited.
The Load-Bearing Mechanosome Revisited.
复制标题
DOI：
10.1007/s12018-010-9075-1
复制
发表时间：
2010-11-11
影响因子：
1.8
通讯作者：
Pavalko, Fredrick M
中科院分区：
文献类型：
--
作者：
Bidwell, Joseph P;Pavalko, Fredrick M
我们在2003年引入了机械体假说作为研究骨中机械转导的启发式模型（Pavalko等人，J Cell Biochem，2003，88（1）：104-112）。该模型提出了研究机械信息如何从传感器骨细胞的膜传递到靶基因的具体方法，以及这种从膜传递的信息如何转化为转录的变化。机械体假说的关键概念是，载荷引起的骨骼变形会使传感器细胞膜变形;嵌入膜中的是粘着斑和钙粘蛋白-连环蛋白复合物，它们又通过固态支架与染色质物理连接。膜的物理刺激从粘附平台发射多蛋白复合物（机械小体），同时将靶基因拖到与传入的机械小体接触的位置，机械小体是机械信息到细胞核的载体。机械小体由粘附相关蛋白和核质穿梭转录因子组成。当到达靶基因时，机械小体改变DNA构象，从而影响基因沿着反式作用蛋白之间的相互作用，改变基因活性。在这里，我们更新了自我们最初的假设发表以来与机械体概念相关的重大进展。粘附和细胞内分泌相关蛋白向细胞核中靶基因的发射似乎是调节细胞对其机械微环境变化的反应的常见机制。
We introduced the mechanosome hypothesis in 2003 as a heuristic model for investigating mechanotransduction in bone (Pavalko et al., J Cell Biochem, 2003, 88(1):104–112). This model suggested specific approaches for investigating how mechanical information is conveyed from the membrane of the sensor bone cell to the target genes and how this transmitted information from the membrane is converted into changes in transcription. The key concepts underlying the mechanosome hypothesis are that load-induced deformation of bone deforms the sensor cell membrane; embedded in the membrane are the focal adhesion and cadherin–catenin complexes, which in turn are physically connected to the chromatin via a solid-state scaffold. The physical stimulation of the membrane launches multiprotein complexes (mechanosomes) from the adhesion platforms while concomitantly tugging target genes into position for contact with the incoming mechanosomes, the carriers of the mechanical information to the nucleus. The mechanosome is comprised of an adhesion-associated protein and a nucleocytoplasmic shuttling transcription factor. Upon arrival at the target gene, mechanosomes alter DNA conformation and thus influence the interactions between trans-acting proteins along the gene, changing gene activity. Here, we update significant progress related to the mechanosome concept since publication of our original hypothesis. The launching of adhesion- and cytoskeletal-associated proteins into the nucleus toward target genes appears to be a common mechanism for regulating cell response to changes in its mechanical microenvironment.