A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts
A role for β-dystroglycan in the organization and structure of the nucleus in myoblasts
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DOI：
10.1016/j.bbamcr.2012.11.019
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发表时间：
2013-03-01
影响因子：
5.1
通讯作者：
Cisneros, Bulmaro
中科院分区：
文献类型：
--
作者：
Martinez-Vieyra, Ivette A.;Vasquez-Limeta, Alejandra;Cisneros, Bulmaro
我们最近描述了β -三磷酸腺苷的核输入途径；然而，它的核作用仍然未知。在这项研究中，我们首次证明了β -三聚糖聚糖与来自不同核室的不同蛋白质的相互作用，包括核膜（NE） （emerin和层粘胶蛋白A/C和B1）、剪接斑点（SC35）、Cajal小体（p80-coilin）和核仁（Nopp140）。电镜分析显示-三磷酸腺苷定位于核膜、核质和核仁。有趣的是，β -糖异常蛋白的下调会导致emerin和层粘连蛋白B1的错定位和表达减少，但不会导致层粘连蛋白A/C的表达减少，也会导致核仁、Cajal小体和剪接斑点的破坏，同时Nopp140和p80-coilin的水平降低，但SC35的水平不会降低。定量反转录PCR和环己亚胺介导的蛋白阻滞实验显示，β -三磷酸腺苷缺陷不改变NE蛋白emerin的mRNA表达，但改变了NE蛋白的稳定性，加速了蛋白的周转。此外，β -三聚糖异常蛋白的敲低破坏了NE介导的过程，包括核形态和中心体-核连锁，这提供了β -三聚糖异常蛋白与NE蛋白的关联具有生物学相关性的证据。出乎意料的是，β -糖醛酸失调的细胞表现出多个中心体，这是癌细胞的一个特征。总之，这些发现表明β -三磷酸腺苷是一种参与核组织和NE结构和功能的核支架蛋白，可能是核包膜生物发生的一个贡献者。(c) 2012 Elsevier B.V.版权所有
We recently characterized a nuclear import pathway for beta-dystroglycan; however, its nuclear role remains unknown. In this study, we demonstrate for the first time, the interaction of beta-dystroglycan with distinct proteins from different nuclear compartments, including the nuclear envelope (NE) (emerin and lamins A/C and B1), splicing speckles (SC35), Cajal bodies (p80-coilin), and nucleoli (Nopp140). Electron microscopy analysis revealed that beta-dystroglycan localized in the inner nuclear membrane, nucleoplasm, and nucleoli. Interestingly, downregulation of beta-dystroglycan resulted in both mislocalization and decreased expression of emerin and lamin B1, but not lamin A/C, as well in disorganization of nucleoli, Cajal bodies, and splicing speckles with the concomitant decrease in the levels of Nopp140, and p80-coilin, but not SC35. Quantitative reverse transcription PCR and cycloheximide-mediated protein arrest assays revealed that beta-dystroglycan deficiency did not change mRNA expression of NE proteins emerin and lamin B1 bud did alter their stability, accelerating protein turnover. Furthermore, knockdown of beta-dystroglycan disrupted NE-mediated processes including nuclear morphology and centrosome-nucleus linkage, which provides evidence that beta-dystroglycan association with NE proteins is biologically relevant. Unexpectedly, beta-dystroglycan-depleted cells exhibited multiple centrosomes, a characteristic of cancerous cells. Overall, these findings imply that beta-dystroglycan is a nuclear scaffolding protein involved in nuclear organization and NE structure and function, and that might be a contributor to the biogenesis of nuclear envelopathies. (c) 2012 Elsevier B.V. All rights reserved.