A mechanistic model for the organization of microtubule asters by motor and non-motor proteins in a mammalian mitotic extract
A mechanistic model for the organization of microtubule asters by motor and non-motor proteins in a mammalian mitotic extract
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DOI：
10.1091/mbc.e03-08-0579
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发表时间：
2004-05-01
影响因子：
3.3
通讯作者：
Compton, DA
中科院分区：
文献类型：
--
作者：
Chakravarty, A;Howard, L;Compton, DA
我们使用计算机模拟来了解参与微管aster组织的马达（动力蛋白，HSET和Eg5）和非马达（NuMA）蛋白之间的功能关系。该模拟准确地预测微管组织下的所有组合的电机和非电机蛋白，提供微管交联在负端是动态的，动力蛋白和HSET仅限于交联微管在平行方向。从这些数据中得到一个机械模型，其中两个聚集体性质的组合，净负端定向力和微管交联取向偏差，确定微管组织。该模型使用电机和非电机蛋白，占电机拮抗作用，并预测，微管交联方向偏差的改变应补偿在微管星形形成的电机力的不平衡。我们在哺乳动物有丝分裂提取物中测试了这一预测，并与模型一致，发现增加NuMA对微管交联的贡献弥补了Eg5运动活性的丧失。因此，该模型提出了每个非中心体的精确作用机制。蛋白质在微管aster组织，并建议微管组织中的纺锤体涉及运动力从电机和静态力从非电机交联蛋白质。
We used computer simulation to understand the functional relationships between motor (dynein, HSET, and Eg5) and non-motor (NuMA) proteins involved in microtubule aster organization. The simulation accurately predicted microtubule organization under all combinations of motor and non-motor proteins, provided that microtubule cross-links at minus-ends were dynamic, and dynein and HSET were restricted to cross-linking microtubules in parallel orientation only. A mechanistic model was derived from these data in which a combination of two aggregate properties, Net Minus-end-directed Force and microtubule Cross-linking Orientation Bias, determine microtubule organization. This model uses motor and non-motor proteins, accounts for motor antagonism, and predicts that alterations in microtubule Cross-linking Orientation Bias should compensate for imbalances in motor force during microtubule aster formation. We tested this prediction in the mammalian mitotic extract and, consistent with the model, found that increasing the contribution of microtubule cross-linking by NuMA compensated for the loss of Eg5 motor activity. Thus, this model proposes a precise mechanism of action of each noncentrosomal. protein during microtubule aster organization and suggests that microtubule organization in spindles involves both motile forces from motors and static forces from non-motor cross-linking proteins.