RESUMO
Lamins are the major structural components of the nuclear lamina found in metazoan organisms. Extensive studies using tissue culture cells have shown that lamins are involved in a wide range of basic cell functions. This has led to the prevailing idea that a given animal cell needs at least one lamin protein for its basic proliferation and survival. However, recent studies have shown that lamins are dispensable for the proliferation and survival of mouse embryonic stem cells (ESC). In contrast to a lack of essential functions in ESCs, certain differentiated cells lacking B-type lamins exhibit increased cell cycle exit rates and enhanced senescence. In this Extra View, we discuss how studies using animal models and cell cultures have begun to reveal cell-type specific functions of lamins in tissue building and homeostasis.
Assuntos
Laminas/metabolismo , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Caenorhabditis elegans/metabolismo , Proliferação de Células , Sobrevivência Celular , Drosophila/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Lamina Tipo A/metabolismo , Lamina Tipo B/metabolismo , Laminas/antagonistas & inibidores , Laminas/genética , Camundongos , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Interferência de RNARESUMO
The genome is virtually identical in all cells within an organism, with epigenetic changes contributing largely to the plasticity in gene expression during both development and aging. These changes include covalent modifications of chromatin components and altered chromatin organization as well as changes in other nuclear components, such as nuclear envelope lamins. Given that DNA in each chromosome is centimeters long and dozens of chromosomes are compacted into a microns-diameter nucleus through non-trivial interactions with the bounding envelope, the polymer physics of such a structure under stress can be complex but perhaps systematic. We summarize micromanipulation methods for measuring the physical plasticity of the nucleus, with recent studies documenting the extreme flexibility of human embryonic stem cells and the rigidification in model aging of progerin-type nuclei. Lamin-A/C is a common molecular factor, and methods are presented for its knockdown and measurement.
Assuntos
Núcleo Celular/química , Núcleo Celular/fisiologia , Técnicas Citológicas/métodos , Animais , Núcleo Celular/genética , Técnicas de Silenciamento de Genes/métodos , Humanos , Laminas/antagonistas & inibidores , Laminas/genética , Modelos Biológicos , Modelos Teóricos , Membrana Nuclear/química , Membrana Nuclear/fisiologia , Organismos Geneticamente Modificados , Interferência de RNA/fisiologiaRESUMO
Functions of nuclear polymeric proteins such as lamin A/C and actin in transport of plasmid DNA were studied. The results show that the lamina plays an important role in plasmid DNA's entry into the cell nucleus from the cytoplasm. Selective disruption of lamin A/C led to a halt in plasmid DNA transport through the nuclear envelope. Inside the nucleus, plasmid DNA was frequently localized at sites with impaired genome integrity, such as DNA double-strand breaks (DSBs), occurring spontaneously or induced by ionizing radiation. Polymeric actin obviously participates in nuclear transport of plasmid DNA, since inhibition of actin polymerization by latrunculin B disturbed plasmid transport inside the cell nucleus. In addition, precluding of actin polymerization inhibited plasmid co-localization with newly induced DSBs. These findings indicate the crucial role of polymeric actin in intranuclear plasmid transport.
