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后期B模型:三种有丝分裂马达蛋白在从极向流到纺锤体伸长转变中的作用

Model for anaphase B: role of three mitotic motors in a switch from poleward flux to spindle elongation.

作者信息

Brust-Mascher I, Civelekoglu-Scholey G, Kwon M, Mogilner A, Scholey J M

机构信息

Laboratory of Cell and Computational Biology, Center for Genetics and Development, University of California, Davis, CA 95616, USA.

出版信息

Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15938-43. doi: 10.1073/pnas.0407044101. Epub 2004 Nov 2.

Abstract

It has been proposed that the suppression of poleward flux within interpolar microtubule (ipMT) bundles of Drosophila embryonic spindles couples outward forces generated by a sliding filament mechanism to anaphase spindle elongation. Here, we (i) propose a molecular mechanism in which the bipolar kinesin KLP61F persistently slides dynamically unstable ipMTs outward, the MT depolymerase KLP10A acts at the poles to convert ipMT sliding to flux, and the chromokinesin KLP3A inhibits the depolymerase to suppress flux, thereby coupling ipMT sliding to spindle elongation; (ii) used KLP3A inhibitors to interfere with the coupling process, which revealed an inverse linear relation between the rates of flux and elongation, supporting the proposed mechanism and demonstrating that the suppression of flux controls both the rate and onset of spindle elongation; and (iii) developed a mathematical model using force balance and rate equations to describe how motors sliding the highly dynamic ipMTs apart can drive spindle elongation at a steady rate determined by the extent of suppression of flux.

摘要

有人提出,果蝇胚胎纺锤体的极间微管(ipMT)束内的极向通量抑制将滑动丝机制产生的向外力与后期纺锤体伸长联系起来。在这里,我们(i)提出了一种分子机制,其中双极驱动蛋白KLP61F持续向外滑动动态不稳定的ipMT,MT解聚酶KLP10A在两极起作用将ipMT滑动转化为通量,而染色体驱动蛋白KLP3A抑制解聚酶以抑制通量,从而将ipMT滑动与纺锤体伸长联系起来;(ii)使用KLP3A抑制剂干扰耦合过程,这揭示了通量速率和伸长速率之间的反比线性关系,支持了所提出的机制,并证明通量的抑制控制了纺锤体伸长的速率和起始;(iii)使用力平衡和速率方程开发了一个数学模型,以描述将高度动态的ipMT拉开的马达如何以由通量抑制程度决定的稳定速率驱动纺锤体伸长。

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本文引用的文献

1
A standardized kinesin nomenclature.一种标准化的驱动蛋白命名法。
J Cell Biol. 2004 Oct 11;167(1):19-22. doi: 10.1083/jcb.200408113.
5
Cell division.细胞分裂
Nature. 2003 Apr 17;422(6933):746-52. doi: 10.1038/nature01599.
8
Force production by single kinesin motors.单个驱动蛋白马达产生的力。
Nat Cell Biol. 2000 Oct;2(10):718-23. doi: 10.1038/35036345.

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