Gönczy P, Bellanger J M, Kirkham M, Pozniakowski A, Baumer K, Phillips J B, Hyman A A
Swiss Institute for Experimental Cancer Research, Lausanne.
Dev Cell. 2001 Sep;1(3):363-75. doi: 10.1016/s1534-5807(01)00046-6.
Proper spindle positioning is essential for spatial control of cell division. Here, we show that zyg-8 plays a key role in spindle positioning during asymmetric division of one-cell stage C. elegans embryos by promoting microtubule assembly during anaphase. ZYG-8 harbors a kinase domain and a domain related to Doublecortin, a microtubule-associated protein (MAP) affected in patients with neuronal migration disorders. Sequencing of zyg-8 mutant alleles demonstrates that both domains are essential for function. ZYG-8 binds to microtubules in vitro, colocalizes with microtubules in vivo, and promotes stabilization of microtubules to drug or cold depolymerization in COS-7 cells. Our findings demonstrate that ZYG-8 is a MAP crucial for proper spindle positioning in C. elegans, and indicate that the function of the Doublecortin domain in modulating microtubule dynamics is conserved across metazoan evolution.
正确的纺锤体定位对于细胞分裂的空间控制至关重要。在此,我们表明,zyg-8在秀丽隐杆线虫单细胞期胚胎不对称分裂过程中的纺锤体定位中起关键作用,它通过在后期促进微管组装来实现这一功能。ZYG-8含有一个激酶结构域和一个与双皮质素相关的结构域,双皮质素是一种微管相关蛋白(MAP),在患有神经元迁移障碍的患者中受到影响。对zyg-8突变等位基因的测序表明,这两个结构域对于其功能都是必不可少的。ZYG-8在体外与微管结合,在体内与微管共定位,并促进COS-7细胞中微管对药物或冷解聚的稳定性。我们的研究结果表明,ZYG-8是秀丽隐杆线虫中正确纺锤体定位所必需的一种微管相关蛋白,并表明双皮质素结构域在调节微管动力学方面的功能在整个后生动物进化过程中是保守的。