Self-organization of cellular structures induced by the overexpression of nuclear envelope proteins: a correlative light and electron microscopy study

Abstract

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.