Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish
Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish
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DOI：
10.1128/mcb.01181-14
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Xiaojie Yang;Qilin Gu;Li Lin;Shaoyang Li;Shan Zhong;Qing Li;Zongbin Cui
中科院分区：
文献类型：
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作者：
Xiaojie Yang;Qilin Gu;Li Lin;Shaoyang Li;Shan Zhong;Qing Li;Zongbin Cui
核孔蛋白p62 （Nup62）定位于核孔复合物（NPCs）的中央通道，调节核孔通透性和核胞质运输。然而，Nup62在脊椎动物中的发育作用仍不清楚。斑马鱼Nup62样蛋白（Nup62l）是哺乳动物Nup62的同源物。nup62l基因在母体中表达，但其转录本在胚胎早期普遍存在，并在发育中的胚胎的头部、咽和肠中富集。激活Wnt/β-catenin通路可正向调节nup62l的转录，而Bmp信号传导作用于Wnt/β-catenin信号传导的下游，负向调节nup62l的表达。过表达nup621l的背化胚胎和增强原肠胚的收敛和伸展（CE）运动。相反，nup621l基因敲低导致胚胎腹侧化，CE运动障碍，中线器官祖细胞发育缺陷。从机制上讲，Nup62l通过与斑马鱼β-catenin-1/2的核输入相互作用和促进Wnt/β-catenin信号的激活剂。因此，Nup62l通过介导斑马鱼β-catenins的核输入来调节背腹侧模式、原肠胚CE运动和中线器官前体的适当规范。
ABSTRACT Nucleoporin p62 (Nup62) localizes in the central channel of nuclear pore complexes (NPCs) and regulates nuclear pore permeability and nucleocytoplasmic transport. However, the developmental roles of Nup62 in vertebrates remain largely unclear. Zebrafish Nup62-like protein (Nup62l) is a homolog of mammalian Nup62. The nup62l gene is maternally expressed, but its transcripts are ubiquitously distributed during early embryogenesis and enriched in the head, pharynx, and intestine of developing embryos. Activation of the Wnt/β-catenin pathway positively modulates nup62l transcription, while Bmp signaling acts downstream of Wnt/β-catenin signaling to negatively regulate nup62l expression. Overexpression of nup62l dorsalized embryos and enhanced gastrula convergence and extension (CE) movements. In contrast, knockdown of Nup62l led to ventralized embryos, an impediment to CE movements, and defects in specification of midline organ progenitors. Mechanistically, Nup62l acts as an activator of Wnt/β-catenin signaling through interaction with and facilitation of nuclear import of β-catenin-1/2 in zebrafish. Thus, Nup62l regulates dorsoventral patterning, gastrula CE movements, and proper specification of midline organ precursors through mediating the nuclear import of β-catenins in zebrafish.