Samp1 is functionally associated with the LINC complex and A-type lamina networks
Samp1 is functionally associated with the LINC complex and A-type lamina networks
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DOI：
10.1242/jcs.078923
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发表时间：
2011-06-15
影响因子：
4
通讯作者：
Hallberg, Einar
中科院分区：
文献类型：
--
作者：
Gudise, Santhosh;Figueroa, Ricardo A.;Hallberg, Einar
跨膜内核膜（INM）蛋白Samp 1是锚定中心体在细胞核附近所必需的。使用高分辨率荧光显微镜，我们发现，Samp 1是分布在一个独特的和特征性的模式在核膜（NE），在那里它部分共定位与LINC复合蛋白Sun 1。通过研究Samp 1缺失突变体和融合蛋白的定位，我们得出结论，Samp 1的N-末端富含半胱氨酸的一半是核质暴露的，负责靶向INM。它含有四个保守的CxxC基序，具有形成锌指的潜力。半胱氨酸到丙氨酸取代突变体，旨在防止锌指形成的分布表明，NE本地化的Samp 1依赖于完整的CxxC基序。Samp 1锌指突变体的过表达产生了一种异常的显性表型，其特征是选择性NE蛋白亚群的组织被破坏，包括Emerin、Sun 1、内源性Samp 1，在某些情况下，还有核纤层蛋白A/C，但不包括核纤层蛋白B、Sun 2或核孔蛋白。Samp 1表达的沉默表明Emerin依赖于Samp 1在NE中的正确定位。我们的研究结果表明，Samp 1与LINC复合蛋白Sun 1和A型纤层网络蛋白在功能上相关。
The transmembrane inner nuclear membrane (INM) protein Samp1 is required for anchoring centrosomes near the nuclei. Using high-resolution fluorescence microscopy we show that Samp1 is distributed in a distinct and characteristic pattern in the nuclear envelope (NE), where it partially colocalizes with the LINC complex protein Sun1. By studying the localization of Samp1 deletion mutants and fusion proteins, we conclude that the cysteine-rich N-terminal half of Samp1 is nucleoplasmically exposed and is responsible for targeting to the INM. It contains four conserved CxxC motifs with the potential to form zinc fingers. The distribution of cysteine-to-alanine substitution mutants, designed to prevent zinc finger formation, showed that NE localization of Samp1 depends on intact CxxC motifs. Overexpression of Samp1 zinc finger mutants produced an abnormal dominant phenotype characterized by disrupted organization of a selective subset NE proteins, including emerin, Sun1, endogenous Samp1 and, in some cases, lamin A/C, but not lamin B, Sun2 or nucleoporins. Silencing of Samp1 expression showed that emerin depends on Samp1 for its correct localization in the NE. Our results demonstrate that Samp1 is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network.