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Abstract：
Cells actively position their nuclei within the cytoplasm for multiple cellular and physiological functions.1-3 Consequently, nuclear mispositioning is usually associated with cell dysfunction and disease, from muscular disorders to cancer metastasis.4-7 Different cell types position their nuclei away from the leading edge during cell migration.8-11 In migrating fibroblasts, nuclear positioning is driven by an actin retrograde flow originated at the leading edge that drives dorsal actin cables away from the leading edge. The dorsal actin cables connect to the nuclear envelope by the linker of nucleoskeleton and cytoskeleton (LINC) complex on transmembrane actin-associated nuclear (TAN) lines.12-14 Dorsal actin cables are required for the formation of TAN lines. How dorsal actin cables are organized to promote TAN lines formation is unknown. Here, we report a role for Ctdnep1/Dullard, a nuclear envelope phosphatase,15-22 and the actin regulator Eps8L223-25 on nuclear positioning and cell migration. We demonstrate that Ctdnep1 and Eps8L2 directly interact, and this interaction is important for nuclear positioning and cell migration. We also show that Ctdnep1 and Eps8L2 are involved in the formation and thickness of dorsal actin cables required for TAN lines engagement during nuclear movement. We propose that Ctdnep1-Eps8L2 interaction regulates dorsal actin cables for nuclear movement during cell migration.
摘要：
细胞积极地将它们的细胞核定位在细胞质中，以实现多种细胞和生理功能。1-3因此，核定位错误通常与细胞功能障碍和疾病相关，从肌肉疾病到癌症转移4-7在细胞迁移过程中，不同的细胞类型将细胞核定位为远离前缘8-11在迁移成纤维细胞中，核定位是由源自前缘的肌动蛋白逆行流驱动的，该逆行流驱动背侧肌动蛋白电缆远离前缘。背侧肌动蛋白电缆通过跨膜肌动蛋白相关核（TAN）线上的核骨架和细胞骨架（LINC）复合物的接头连接到核被膜。12-14背侧肌动蛋白电缆是形成TAN线所必需的。背侧肌动蛋白电缆如何组织以促进TAN线形成尚不清楚。这里,我们报告了Ctdnep1/Dullard的作用，一种核包膜磷酸酶,15-22和肌动蛋白调节剂Eps8L223-25对核定位和细胞迁移的影响。我们证明了Ctdnep1和Eps8L2直接相互作用，这种相互作用对细胞核定位和细胞迁移很重要。我们还表明，Ctdnep1和Eps8L2参与了核运动过程中TAN线接合所需的背侧肌动蛋白电缆的形成和厚度。我们建议Ctdnep1-Eps8L2相互作用调节背侧肌动蛋白电缆在细胞迁移过程中的核运动。
