Redundant mechanisms recruit actin into the contractile ring in silkworm spermatocytes.
Redundant mechanisms recruit actin into the contractile ring in silkworm spermatocytes.
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DOI：
10.1371/journal.pbio.0060209
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发表时间：
2008-09-02
期刊：
影响因子：
9.8
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Chen W;Foss M;Tseng KF;Zhang D
胞质分裂由新组装的收缩环内的肌动球蛋白丝的收缩提供动力。微管是诱导胞质分裂所必需的纺锤体成分。这种诱导可以使用中央纺锤体和/或星形微管来刺激纺锤体赤道周围的皮质收缩（赤道刺激）。或者，或者另外，诱导可能依赖于星形微管来放松极地皮层（极地放松）。为了研究微管、皮质硬度和收缩环组装之间的关系，我们使用不同构型的微管来操纵肌动蛋白在家蚕精母细胞中的分布。机械重新定位，noninterdigitating微管可以诱导再分配的肌动蛋白在任何区域的皮质局部排除皮质肌动蛋白丝。这种肌动蛋白的皮层流动促进了局部的放松，同时增加了其他地方的张力（通常在赤道皮层）。与此相反，重新定位的交错微管束使用一种新的机制，以诱导局部刺激皮层内的任何地方的收缩性，在中央纺锤体微管的反平行加端，肌动蛋白聚集体迅速组装从头和横向运输到赤道皮层。松弛依赖于微管动力学，但不依赖于RhoA活性，而刺激依赖于RhoA活性，但在很大程度上是独立的微管动力学。我们的结论是，极性松弛和赤道刺激机制冗余供应肌动蛋白收缩环组装，从而增加了保真度的分裂。在动物细胞中，细胞分裂的最后一步，或者说胞质分裂，需要一个收缩环的作用，这个收缩环主要由肌动蛋白和肌球蛋白的促动剂组成，它将细胞一分为二。在细胞分裂之前，它首先复制其基因组并将染色体分离成两个新形成的子细胞，这是由一种称为纺锤体的结构完成的任务，该结构主要由称为微管的长聚合物组成。分裂的位点必须发生在分离的染色体之间--纺锤体赤道处--以确保每个细胞获得正确数量的染色体。除了分离染色体外，微管也是诱导减数分裂的关键，但它们是如何做到这一点的还存在争议。例如，“极地松弛”假说提出，向外辐射的星形微管导致收缩元素从极地皮层流向赤道，从而导致沟槽。相反，“赤道刺激”假说提出纺锤体微管直接刺激卵裂只在赤道。使用一种新的方法，我们证明这两种机制实际上共同发挥作用，将肌动蛋白丝招募到新生环中，提供冗余，提高保真度。具体来说，我们能够机械地改变肌动蛋白丝在活的分裂细胞中的分布，通过使用显微镜针头操纵微管，同时用化学化合物扰乱细胞骨架。我们的高分辨率显微镜数据推进了对这两种机制的理解。我们还记录了一种新的，微管为基础的机制，运输肌动蛋白聚集体的赤道皮质。这些结果有助于解决关于这一基本细胞过程的长期争议。在胞质分裂过程中肌动蛋白是如何聚集成收缩环的？结合显微操作与药理学扰动，这项全面的研究优雅地记录了一个细胞内两种互补机制的贡献。
Cytokinesis is powered by the contraction of actomyosin filaments within the newly assembled contractile ring. Microtubules are a spindle component that is essential for the induction of cytokinesis. This induction could use central spindle and/or astral microtubules to stimulate cortical contraction around the spindle equator (equatorial stimulation). Alternatively, or in addition, induction could rely on astral microtubules to relax the polar cortex (polar relaxation). To investigate the relationship between microtubules, cortical stiffness, and contractile ring assembly, we used different configurations of microtubules to manipulate the distribution of actin in living silkworm spermatocytes. Mechanically repositioned, noninterdigitating microtubules can induce redistribution of actin at any region of the cortex by locally excluding cortical actin filaments. This cortical flow of actin promotes regional relaxation while increasing tension elsewhere (normally at the equatorial cortex). In contrast, repositioned interdigitating microtubule bundles use a novel mechanism to induce local stimulation of contractility anywhere within the cortex; at the antiparallel plus ends of central spindle microtubules, actin aggregates are rapidly assembled de novo and transported laterally to the equatorial cortex. Relaxation depends on microtubule dynamics but not on RhoA activity, whereas stimulation depends on RhoA activity but is largely independent of microtubule dynamics. We conclude that polar relaxation and equatorial stimulation mechanisms redundantly supply actin for contractile ring assembly, thus increasing the fidelity of cleavage. In animal cells, the last step of cell division, or cytokinesis, requires the action of a contractile ring—composed largely of actin and myosin filaments—that cleaves the cell in two. Before the cell divides, it first duplicates its genome and separates the chromosomes into the two newly forming daughter cells, a task carried out by a structure called the spindle apparatus, which is composed mostly of long polymers called microtubules. The site of cleavage must occur between the segregating chromosomes—at the spindle equator—to ensure that each cell receives the proper number of chromosomes. In addition to separating the chromosomes, microtubules are also essential for inducing cytokinesis—but how they do this is controversial. For example, the “polar relaxation” hypothesis proposes that the astral microtubules, which radiate outward, cause contractile elements to flow from the polar cortex toward the equator, resulting in furrowing. In contrast, the “equatorial stimulation” hypothesis proposes that the spindle microtubules directly stimulate cleavage exclusively at the equator. Using a novel approach, we demonstrate that both mechanisms are in fact functioning together to recruit actin filaments to the nascent ring, providing redundancy that increases fidelity. Specifically, we were able to mechanically alter the distribution of actin filaments in living, dividing cells by using a microscopic needle to manipulate microtubules while perturbing the cytoskeleton with chemical compounds. Our high-resolution microscopy data advance the understanding of both proposed mechanisms. We also documented a novel, microtubule-based mechanism for transporting actin aggregates to the equatorial cortex. These results help to resolve a long-standing dispute concerning this fundamental cellular process. How is actin recruited to assemble a contractile ring during cytokinesis? Combining micromanipulation with pharmacological perturbation, this comprehensive study elegantly documents the contributions of two complementary mechanisms within one cell.
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DOI：
10.1083/jcb.200301147
发表时间：
2003-06-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Janson ME;de Dood ME;Dogterom M
通讯作者：
Dogterom M
影响因子：
3.3
作者：
Chen, Qian;Lakshmikanth, Gandikota S.;De Lozanne, Arturo
通讯作者：
De Lozanne, Arturo
影响因子：
9.2
作者：
Canman, JC;Hoffman, DB;Salmon, ED
通讯作者：
Salmon, ED
影响因子：
64.8
作者：
Canman, JC;Cameron, LA;Salmon, ED
通讯作者：
Salmon, ED
囊泡和肌动蛋白通过沟微管和中央纺锤体靶向卵裂沟。
DOI：
10.1083/jcb.200803096
发表时间：
2008-06-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Albertson R;Cao J;Hsieh TS;Sullivan W
通讯作者：
Sullivan W