Nuclei migrate through constricted spaces using microtubule motors and actin networks in C-elegans hypodermal cells
Nuclei migrate through constricted spaces using microtubule motors and actin networks in C-elegans hypodermal cells
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DOI：
10.1242/dev.141192
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发表时间：
2016-11-15
期刊：
影响因子：
4.6
通讯作者：
Starr, Daniel A.
中科院分区：
文献类型：
--
作者：
Bone, Courtney R.;Chang, Yu-Tai;Starr, Daniel A.
通过狭窄空间的细胞迁移是许多发育和疾病过程的关键方面，包括造血、炎症和转移。这些事件的一个限制因素是核变形。在这里，我们建立了一个体内模型，其中细胞核可以可视化，而通过收缩移动，并使用它来阐明核迁移的机制。C.秀丽隐杆线虫皮下P细胞幼虫核穿过约为其宽度5%的狭窄空间。这种收缩被纤维细胞器阻止，纤维细胞器是通过P细胞将肌肉连接到角质层的结构。当细胞核和核纤层经历极端的形态变化以挤压通过空间时，纤维细胞器在细胞核迁移之前被移除。肌动蛋白和微管网络都被组织起来介导核迁移。LINC复合物由SUN蛋白质104 -84和KASH蛋白质104 -83组成，将动力蛋白和驱动蛋白-1募集到核表面。这两种马达都在P细胞核迁移中起作用，但动力蛋白通过β-83起作用，在细胞核向极化微管网络的负端迁移时发挥更重要的作用。因此，核骨架和细胞骨架相互协调，使细胞核在狭窄的空间中移动。
Cellular migrations through constricted spaces are a crucial aspect of many developmental and disease processes including hematopoiesis, inflammation and metastasis. A limiting factor in these events is nuclear deformation. Here, we establish an in vivo model in which nuclei can be visualized while moving through constrictions and use it to elucidate mechanisms for nuclear migration. C. elegans hypodermal P-cell larval nuclei traverse a narrow space that is about 5% their width. This constriction is blocked by fibrous organelles, structures that pass through P cells to connect the muscles to cuticle. Fibrous organelles are removed just prior to nuclear migration, when nuclei and lamins undergo extreme morphological changes to squeeze through the space. Both actin and microtubule networks are organized to mediate nuclear migration. The LINC complex, consisting of the SUN protein UNC-84 and the KASH protein UNC-83, recruits dynein and kinesin-1 to the nuclear surface. Both motors function in P-cell nuclear migration, but dynein, functioning through UNC-83, plays a more central role as nuclei migrate towards minus ends of polarized microtubule networks. Thus, the nucleoskeleton and cytoskeleton are coordinated to move nuclei through constricted spaces.