Katsuki Miho, Drummond Douglas R, Cross Robert A
1] Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK [2].
Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Nat Commun. 2014;5:3094. doi: 10.1038/ncomms4094.
Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe.
天然微管通常在呈螺旋对称的B晶格管内包含一条A晶格缝。目前尚不清楚A晶格缝如何影响微管的动态不稳定性。在此我们发现，在GMPCPP微管（动态微管的GTP帽的结构类似物）中加入额外的A晶格缝会使其不稳定，将它们的平均收缩率提高20倍以上。由含有额外A晶格缝的种子成核的动态微管的生长速率与由B晶格种子成核的微管相似，但两端的解聚频率增加。此外，将B晶格GDP微管与僵直驱动蛋白表面结合可使其抵抗收缩而稳定，而具有额外A晶格缝的微管仅略有稳定。我们的数据表明，在动态微管中引入额外的A晶格缝会通过破坏其GTP帽的稳定性而使其不稳定。在此基础上，我们提出天然B晶格微管的单一A晶格缝可能充当解聚的触发点，并且可能是调节点。
Zotero 插件
