Coupling of the nucleus and cytoplasm: role of the LINC complex
Coupling of the nucleus and cytoplasm: role of the LINC complex
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DOI：
10.1083/jcb.200509124
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发表时间：
2006-01-02
影响因子：
7.8
通讯作者：
Hodzic, D
中科院分区：
文献类型：
--
作者：
Crisp, M;Liu, Q;Hodzic, D
核被膜是细胞核和细胞质之间的屏障，其特征是由核周间隙（PNS）分隔的内膜和外膜。内核膜含有特定的整合蛋白，包括Sun 1和Sun 2。虽然外核膜（ONM）与内质网是连续的，但它仍然富含几种完整的膜蛋白，包括nesprin 2 Giant（nesp 2G），一种800 kD的蛋白质，具有NH 2-末端肌动蛋白结合结构域。最近的一项研究（Padmakumar，VC，T. Libotte，W. Lu，H. Zaim，S. Abraham，A. A.作者声明：R.福斯纳和我。卡拉克西索格鲁2005.《细胞科学杂志》118：3419 - 3430）已经表明nesp 2G定位于ONM依赖于与Sunl的相互作用。在这项研究中，我们证实和扩展这些结果，证明太阳1和太阳2有助于nesp 2G本地化。HeLa细胞中这两种蛋白质的共缺失导致ONM相关nesp 2G的丢失，Sun 1内腔结构域的过表达也是如此。两种治疗均导致PNS扩张。这些数据与Padmakumar等人（2005年）的数据一起支持Sun蛋白通过跨越PNS的相互作用将nesprins束缚在ONM中的模型。以这种方式，Sun蛋白和nesprins形成连接核骨架和细胞骨架的复合物（LINC复合物）。
The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A. A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118: 3419 - 3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex).