toca-1 Is in a Novel Pathway That Functions in Parallel with a SUN-KASH Nuclear Envelope Bridge to Move Nuclei in Caenorhabditis elegans
toca-1 Is in a Novel Pathway That Functions in Parallel with a SUN-KASH Nuclear Envelope Bridge to Move Nuclei in Caenorhabditis elegans
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DOI：
10.1534/genetics.112.146589
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发表时间：
2013-01-01
期刊：
影响因子：
3.3
通讯作者：
Starr, Daniel A.
中科院分区：
文献类型：
--
作者：
Chang, Yu-Tai;Dranow, Daniel;Starr, Daniel A.
将细胞核移动到细胞内的位置对许多基本的细胞和发育过程至关重要，包括细胞迁移、分化、受精和细胞极性的建立。SUN和KASH蛋白的桥梁跨越核膜，介导许多核定位事件，但其他途径通过尚未明确的机制独立发挥作用。为了鉴定和描述核迁移的新机制，我们对编码SUN蛋白的unc-84的核迁移缺陷增强突变进行了无偏正向遗传筛选。在秀丽隐杆线虫幼虫中，皮下p细胞核迁移失败导致动物不协调和产卵缺陷。unc-84缺失动物p细胞核迁移过程对温度敏感；unc-84突变体在25度时迁移失败，但在15度时迁移正常。我们假设另一种途径与unc-84途径平行作用，使p细胞核以15度移动。为了支持我们的假设，前向遗传筛选分离出八个emu （unc-84核迁移缺陷的增强子）突变，这些突变仅在零unc-84背景下破坏核迁移。yc20突变体被确定携带toca-1基因突变。TOCA-1的功能是以细胞自主的方式移动p细胞核。TOCA-1在人类中是保守的，它在内吞过程中起成核和组织肌动蛋白的作用。因此，我们发现了一个先前未知的、可能依赖于动作蛋白的通路中的一个参与者，该通路的功能是使细胞核平行于SUN-KASH桥移动。其他鸸鹋突变可能代表了这种新途径的其他组成部分。
Moving the nucleus to an intracellular location is critical to many fundamental cell and developmental processes, including cell migration, differentiation, fertilization, and establishment of cellular polarity. Bridges of SUN and KASH proteins span the nuclear envelope and mediate many nuclear positioning events, but other pathways function independently through poorly characterized mechanisms. To identify and characterize novel mechanisms of nuclear migration, we conducted a nonbiased forward genetic screen for mutations that enhanced the nuclear migration defect of unc-84, which encodes a SUN protein. In Caenorhabditis elegans larvae, failure of hypodermal P-cell nuclear migration results in uncoordinated and egg-laying-defective animals. The process of P-cell nuclear migration in unc-84 null animals is temperature sensitive; at 25 degrees migration fails in unc-84 mutants, but at 15 degrees the migration occurs normally. We hypothesized that an additional pathway functions in parallel to the unc-84 pathway to move P-cell nuclei at 15 degrees. In support of our hypothesis, forward genetic screens isolated eight emu (enhancer of the nuclear migration defect of unc-84) mutations that disrupt nuclear migration only in a null unc-84 background. The yc20 mutant was determined to carry a mutation in the toca-1 gene. TOCA-1 functions to move P-cell nuclei in a cell-autonomous manner. TOCA-1 is conserved in humans, where it functions to nucleate and organize actin during endocytosis. Therefore, we have uncovered a player in a previously unknown, likely actin-dependent, pathway that functions to move nuclei in parallel to SUN-KASH bridges. The other emu mutations potentially represent other components of this novel pathway.