FLN-2 functions in parallel to LINC complexes and Cdc42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans.
FLN-2 functions in parallel to LINC complexes and Cdc42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans.
复制标题
在秀丽隐杆线虫 P 细胞核迁移过程中，FLN-2 与 LINC 复合物和 Cdc42/肌动蛋白通路平行发挥作用。
DOI：
10.1101/2023.08.04.552041
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Starr,DanielA
中科院分区：
文献类型：
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作者：
Ma,Linda;Kuhn,Jonathan;Chang,Yu-Tai;Elnatan,Daniel;Luxton,GWGant;Starr,DanielA
通过狭窄收缩的核迁移对于发育、转移和促炎反应是重要的。在组织培养细胞中进行的研究表明，LINC（核骨架和细胞骨架的连接物）复合物、微管马达、肌动蛋白细胞骨架和核膜修复机制是细胞核通过狭窄空间运动的重要介质。然而，人们对这些机制如何在体内移动细胞核知之甚少。在秀丽隐杆线虫幼虫中，6对皮下P细胞通过体壁肌肉和角质层之间的狭窄空间从外侧位置迁移到腹侧位置。p细胞的核迁移部分是由LINC复合物通过基于微管的途径和独立的基于CDC-42/actin的途径介导的。然而，当LINC复合物和基于肌动蛋白的途径都被敲除时，许多细胞核仍然迁移，这表明存在其他途径。在这里，我们表明FLN-2在介导p细胞核迁移的第三个途径中起作用。FLN-2中的n端肌动蛋白结合域在典型丝蛋白中发现，对于FLN-2的功能是必不可少的，这一点和结构预测表明FLN-2不是一个分化的丝蛋白。FLN-2的免疫球蛋白（Ig）样重复序列4-8是p细胞核迁移所必需的。此外，在缺乏LINC复合物成分unc-84的情况下，fln-2突变体的p细胞核破裂率增加。我们得出结论，FLN-2的功能与LINC复合物和CDC-42/肌动蛋白通路平行，以维持核膜的完整性，使p细胞细胞核通过狭窄的空间移动。
Nuclear migration through narrow constrictions is important for development, metastasis, and pro-inflammatory responses. Studies performed in tissue culture cells have implicated LINC (linker of nucleoskeleton and cytoskeleton) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo. In C. elegans larvae, 6 pairs of hypodermal P cells migrate from lateral to ventral positions through a constricted space between the body wall muscles and the cuticle. P-cell nuclear migration is mediated in part by LINC complexes using a microtubule-based pathway and by an independent CDC-42/actin-based pathway. However, when both LINC complex and actin-based pathways are knocked out, many nuclei still migrate, suggesting the existence of additional pathways. Here we show that FLN-2 functions in a third pathway to mediate P-cell nuclear migration. The predicted N-terminal actin binding domain in FLN-2 that is found in canonical filamins is dispensable for FLN-2 function, this and structural predictions suggest that FLN-2 is not a divergent filamin. The immunoglobulin (Ig)-like repeats 4–8 of FLN-2 were necessary for P-cell nuclear migration. Furthermore, in the absence of the LINC complex component unc-84, fln-2 mutants had an increase in P-cell nuclear rupture. We conclude that FLN-2 functions to maintain the integrity of the nuclear envelope in parallel with the LINC complex and CDC-42/actin-based pathways to move P-cell nuclei through constricted spaces.