Cell：“分子发动机和刹车”作用机制的研究

生物谷

    来自Pennsylvania大学药学院的科学家最近发现，用于维持细胞形状、运动、复制等功能的微管利用了一种分子发动机和刹车蛋白来使其排列成正确结构。如果微管的排列出现偏差，就会导致细胞分裂等基本功能发生错误，从而可能产生癌症或痴呆等疾病。

    这一结果作为封面文章发表在1月份的《Cell》上。细胞和发展生物学助理教授Phong  Tran表示：“在这之前，分子发动机和刹车是分开研究的。而我们的成果能使科学家更全面的看待这一问题。”

    微管能维持各种细胞形状结构，它还能形成对细胞分裂至关重要的纺锤体，此外还是运送代谢废物以及神经传递素等物质的通道。在文章中，科学家们研究了裂殖酵母细胞。结果发现能通过一种叫做klp2p的分子发动机以及一种叫做ase1p的分子刹车之间的滑动平衡来实现微管的端到端稳定结构。先前存在的母体微管能指导新微管的形成，新的微管能顺着母体的方向生长。

    Tran表示：“新的微管就好像在母体微管上行使的火车，而分子发动机就是它的引擎。问题是其中的货物——分子刹车将减缓新生微管的速度。当火车到达轨道末端时，它仍然和母体微管结合在一起。我们发现通过分子发动机和刹车之间的合作，细胞就可以维持微管结构的稳定。”

     而一旦发动机或刹车发生问题，就会导致结构的错误。这将引起多种疾病。（physorg.com）

英文原文：

Crosslinkers and Motors Organize Dynamic Microtubules to Form Stable Bipolar Arrays in Fission Yeast

Marcel E. Janson,1,3 Rose Loughlin,2 Isabelle Loïodice,1 Chuanhai Fu,1 Damian Brunner,2 François J. Nédélec,2, and Phong T. Tran1,

1 Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA
2 Cell Biology and Biophysics Program, European Molecular Biology Laboratory, 69117 Heidelberg, Germany

Summary

Microtubule (MT) nucleation not only occurs from centrosomes, but also in large part from dispersed nucleation sites. The subsequent sorting of short MTs into networks like the mitotic spindle requires molecular motors that laterally slide overlapping MTs and bundling proteins that statically connect MTs. How bundling proteins interfere with MT sliding is unclear. In bipolar MT bundles in fission yeast, we found that the bundler ase1p localized all along the length of antiparallel MTs, whereas the motor klp2p (kinesin-14) accumulated only at MT plus ends. Consequently, sliding forces could only overcome resistant bundling forces for short, newly nucleated MTs, which were transported to their correct position within bundles. Ase1p thus regulated sliding forces based on polarity and overlap length, and computer simulations showed these mechanisms to be sufficient to generate stable bipolar bundles. By combining motor and bundling proteins, cells can thus dynamically organize stable regions of overlap between cytoskeletal filaments.

Introduction

The bundling of MTs is a crucial step in the formation of MT arrays in interphase and mitotic cells. Lateral contacts between MTs are seen in diverse structures like the spindle midzone, axons, developing muscle cells, cilia, and epithelial cells. The polarity of MT contacts is directly related to the function of MT networks in regulating cell polarity: bundles of parallel MTs in axons provide a directional cue for vesicle transport (Heidemann et al., 1981), and antiparallel MT contacts in the spindle-midzone are essential to the bipolarity of the mitotic spindle (Sharp et al., 2000). In general, processes that regulate the polarity of MTs are not well understood. Centrosomes play a role by grouping MT minus ends together such that neighboring MTs in their asters are parallel. Yet in many systems MTs are nucleated from randomly dispersed nucleation sites and can still form polarized arrays (Janson et al., 2005, Mahoney et al., 2006, Murata et al., 2005). Components of mitotic extracts, for example, organize MTs into bipolar arrays in the complete absence of centrosomes (Heald et al., 1996