Regulation of nuclear pore complex conformation by IP(3) receptor activation.
Regulation of nuclear pore complex conformation by IP(3) receptor activation.
复制标题
通过 IP(3) 受体激活调节核孔复合体构象。
DOI：
10.1016/s0006-3495(02)73913-1
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发表时间：
2002
影响因子：
3.4
通讯作者：
Dunn,RobertC
中科院分区：
文献类型：
--
作者：
Moore-Nichols,David;Arnott,Anne;Dunn,RobertC
近年来，人们对核孔复合体的分子结构和功能动力学的研究越来越深入。这些大的、超分子的蛋白质组合形成了跨越细胞核膜的通道，起着核进出口的关键调节作用。从核膜的细胞质表面看，核孔复合体呈现出围绕中央管腔的八重对称环状结构。管腔通常看起来被另一种结构占据，也称为中央颗粒、核运输复合体或核塞。先前的研究表明，对于中等大小的分子(10-40 kDa)，中央颗粒可能在介导钙依赖的跨核膜扩散调节中发挥作用。使用原子力显微镜测量化学固定的非洲爪哇卵母细胞核膜的表面形貌，我们测量了在各种已知改变核钙储存的条件下，中心颗粒在鼻咽腔内的相对位置。这些测量显示，在缺钙条件下，中央颗粒向核膜细胞质表面移动了大的∼9 nm。此外，核三磷酸肌醇受体被特异性激动剂腺苷A激活，导致中央颗粒位置的浓度依赖性移位，其EC50值为∼1.2 nM。在核膜的胞质和核质面上均可观察到鼻咽癌内中央颗粒的移位。用IP3受体激活的特异性抑制剂xestospongin C处理后，这种移位被阻断。这些结果扩展了以前的鼻咽癌构象动力学模型，将中央颗粒位置与IP3敏感的核膜钙库的耗尽联系起来。
In recent years, both the molecular architecture and functional dynamics of nuclear pore complexes (NPCs) have been revealed with increasing detail. These large, supramolecular assemblages of proteins form channels that span the nuclear envelope of cells, acting as crucial regulators of nuclear import and export. From the cytoplasmic face of the nuclear envelope, nuclear pore complexes exhibit an eightfold symmetric ring structure encompassing a central lumen. The lumen often appears occupied by an additional structure alternatively referred to as the central granule, nuclear transport complex, or nuclear plug. Previous studies have suggested that the central granule may play a role in mediating calcium-dependent regulation of diffusion across the nuclear envelope for intermediate sized molecules (10–40 kDa). Using atomic force microscopy to measure the surface topography of chemically fixedXenopuslaevis oocyte nuclear envelopes, we present measurements of the relative position of the central granule within the NPC lumen under a variety of conditions known to modify nuclear Ca2+stores. These measurements reveal a large, ∼9-nm displacement of the central granule toward the cytoplasmic face of the nuclear envelope under calcium depleting conditions. Additionally, activation of nuclear inositol triphosphate (IP3) receptors by the specific agonist, adenophostin A, results in a concentration-dependent displacement of central granule position with an EC50of ∼1.2 nM. The displacement of the central granule within the NPC is observed on both the cytoplasmic and nucleoplasmic faces of the nuclear envelope. The displacement is blocked upon treatment with xestospongin C, a specific inhibitor of IP3receptor activation. These results extend previous models of NPC conformational dynamics linking central granule position to depletion of IP3sensitive nuclear envelope calcium stores.