Volkova Ekaterina G, Kurchashova Svetlana Y, Polyakov Vladimir Y, Sheval Eugene V
Department of Electron Microscopy, Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119991 Moscow, Russia.
J Electron Microsc (Tokyo). 2011;60(1):57-71. doi: 10.1093/jmicro/dfq067. Epub 2010 Oct 6.
The mechanisms by which the supramolecular order is formed inside the cell nucleus remain poorly understood. So far, two major hypotheses - ordered assembly and stochastic self-organization - have been discussed. To determine which mechanism is responsible for the formation of nuclear envelope, cells overexpressing one of the nuclear envelope proteins (lamin A, lamin B1, pom121 or ndc1) were investigated. According to the ordered assembly model, the presence of an excessive amount of a component has no effect in the formation of the normal structure of a nuclear envelope because it is programmed and cannot be distorted. In contrast, according to the self-organization concept, there is no such strictly determined cellular structures, and an excessive amount of even one component will affect the cellular organization. In the present study, formation of a redundant nuclear envelope was observed in the case of lamin B1 and lamin A overexpression. In the case of the nucleoporins pom121 and ndc1, no incorporation of the overexpressed proteins into the nuclear envelope was observed on the first day after transfection; however, the remodeling of endoplasmic reticulum elements and the formation of membrane aggregates in the cytoplasm were observed. After mitosis, pom121 from the cytoplasmic aggregates was translocated into the redundant nuclear envelope in which it induced inner nuclear membrane protrusions. Therefore, our results indicate that the formation of the nuclear envelope is not predetermined and that an excessive amount of even one protein component can affect cellular structure formation. This study concluded that nuclear envelope formation is achieved by the self-organization mechanism.
细胞核内超分子秩序形成的机制仍知之甚少。到目前为止,已经讨论了两种主要假说——有序组装和随机自组织。为了确定哪种机制负责核膜的形成,研究了过表达核膜蛋白之一(核纤层蛋白A、核纤层蛋白B1、Pom121或Ndc1)的细胞。根据有序组装模型,过量的一种成分的存在对核膜正常结构的形成没有影响,因为它是程序化的,不会被扭曲。相比之下,根据自组织概念,不存在如此严格确定的细胞结构,即使一种成分过量也会影响细胞组织。在本研究中,在核纤层蛋白B1和核纤层蛋白A过表达的情况下观察到了多余核膜的形成。在核孔蛋白Pom121和Ndc1的情况下,转染后第一天未观察到过表达的蛋白质掺入核膜;然而,观察到内质网元件的重塑和细胞质中膜聚集体的形成。有丝分裂后,来自细胞质聚集体的Pom121被转运到多余的核膜中,在其中它诱导了内核膜突起。因此,我们的结果表明核膜的形成不是预先确定的,即使一种蛋白质成分过量也会影响细胞结构的形成。这项研究得出结论,核膜的形成是通过自组织机制实现的。