The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction.
The Molecular Basis and Biologic Significance of the β-Dystroglycan-Emerin Interaction.
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DOI：
10.3390/ijms21175944
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发表时间：
2020-08-19
影响因子：
5.6
通讯作者：
Cisneros B
中科院分区：
文献类型：
--
作者：
Gómez-Monsivais WL;Monterrubio-Ledezma F;Huerta-Cantillo J;Mondragon-Gonzalez R;Alamillo-Iniesta A;García-Aguirre I;Azuara-Medina PM;Arguello-García R;Rivera-Monroy JE;Holaska JM;Hernández-Méndez JME;Garrido E;Magaña JJ;Winder SJ;Brancaccio A;Martínez-Vieyra I;Navarro-Garcia F;Cisneros B
β-肌营养不良蛋白聚糖（β-DG）与核纤层蛋白A/C和B1以及核突蛋白在核膜（NE）处组装以维持适当的核结构和功能。为了深入了解β-DG的核功能，我们在分子水平上表征了β-DG与emerin之间的相互作用。Emerin是调节多个核过程的主要NE蛋白，并且其缺乏导致Emery-Dreifuss肌营养不良症（EDMD）。使用β-DG和emerin的截短变体，通过一系列体外和体内结合实验以及定制的计算分析，我们确定β-DG-emerin相互作用至少部分由它们各自的跨膜结构域（TM）介导。使用表面等离子体共振测定，我们表明，Emerin结合β-DG具有高亲和力（KD在纳摩尔范围内）。值得注意的是，对DG敲除的细胞的分析表明，β-DG的丢失导致了emerin稳定性的降低和emerin介导的过程的损害。β-DG和Emerin对于它们在NE内的最佳靶向是必需的，如通过使用EDMD患者的TM结构域中具有突变的Emerin变体和B淋巴细胞的免疫荧光、蛋白质印迹和免疫沉淀测定所示。总之，我们证明了β-DG作为emerin相互作用伴侣调节其稳定性和功能。
β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery–Dreifuss muscular dystrophy (EDMD). Using truncated variants of β-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the β-DG–emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to β-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of β-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. β-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that β-DG plays a role as an emerin interacting partner modulating its stability and function.
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影响因子：
14.8
作者：
Kozakov D;Hall DR;Xia B;Porter KA;Padhorny D;Yueh C;Beglov D;Vajda S
通讯作者：
Vajda S
DOI：
10.1083/jcb.122.4.809
发表时间：
1993-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ervasti JM;Campbell KP
通讯作者：
Campbell KP
DOI：
10.1016/j.bbamcr.2012.11.019
发表时间：
2013-03-01
影响因子：
5.1
作者：
Martinez-Vieyra, Ivette A.;Vasquez-Limeta, Alejandra;Cisneros, Bulmaro
通讯作者：
Cisneros, Bulmaro
影响因子：
11.4
作者：
Markiewicz, Ewa;Tilgner, Katarzyna;Hutchison, Christopher J.
通讯作者：
Hutchison, Christopher J.
影响因子：
4
作者：
Berk, Jason M.;Simon, Dan N.;Wilson, Katherine L.
通讯作者：
Wilson, Katherine L.