Floch Aurélie G, Palancade Benoit, Doye Valérie
Institut Jacques Monod, CNRS, UMR 7592, Univ. Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France; Ecole Doctorale Gènes Génomes Cellules, Université Paris Sud-11, Orsay, France.
Institut Jacques Monod, CNRS, UMR 7592, Univ. Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France.
Methods Cell Biol. 2014;122:1-40. doi: 10.1016/B978-0-12-417160-2.00001-1.
Nuclear pore complexes (NPCs) are multiprotein assemblies embedded within the nuclear envelope and involved in the control of the bidirectional transport of proteins and ribonucleoparticles between the nucleus and the cytoplasm. Since their discovery more than 50 years ago, NPCs and nucleocytoplasmic transport have been the focus of intense research. Here, we review how the use of a multiplicity of structural, biochemical, genetic, and cell biology approaches have permitted the deciphering of the main features of this macromolecular complex, its mode of assembly as well as the rules governing nucleocytoplasmic exchanges. We first present the current knowledge of the ultrastructure of NPCs, which reveals that they are modular and repetitive assemblies of subunits referred to as nucleoporins, associated into stable subcomplexes and composed of a limited set of protein domains, including phenylalanine-glycine (FG) repeats and membrane-interacting domains. The outcome of investigations on nucleocytoplasmic trafficking will then be detailed, showing how it involves a limited number of molecular factors and common mechanisms, namely (i) indirect association of cargos with nuclear pores through receptors in the donor compartment, (ii) progression within the channel through dynamic hydrophobic interactions with FG-Nups, and (iii) NTPase-driven remodeling of transport complexes in the target compartment. Finally, we also discuss the outcome of more recent studies, which indicate that NPCs and the transport machinery are dynamic and versatile devices, whose biogenesis is tightly coordinated with the cell cycle, and which carry nonconventional duties, in particular, in mitosis, gene expression, and genetic stability.
核孔复合体（NPCs）是嵌入核膜的多蛋白组装体，参与控制蛋白质和核糖核蛋白在细胞核与细胞质之间的双向运输。自50多年前被发现以来，核孔复合体和核质运输一直是深入研究的焦点。在此，我们综述了如何通过多种结构、生化、遗传和细胞生物学方法来解读这种大分子复合体的主要特征、其组装模式以及核质交换的调控规则。我们首先介绍核孔复合体超微结构的现有知识，这表明它们是由被称为核孔蛋白的亚基组成的模块化和重复性组装体，这些亚基结合形成稳定的亚复合体，并由有限的一组蛋白质结构域组成，包括苯丙氨酸 - 甘氨酸（FG）重复序列和膜相互作用结构域。随后将详细阐述核质运输研究的结果，展示其如何涉及有限数量的分子因子和共同机制，即（i）货物通过供体区室中的受体与核孔间接结合，（ii）通过与FG核孔蛋白的动态疏水相互作用在通道内前进，以及（iii）NTPase驱动靶区室中运输复合体的重塑。最后，我们还讨论了最近研究的结果，这些结果表明核孔复合体和运输机制是动态且多功能的装置，其生物发生与细胞周期紧密协调，并且承担着非常规职责，特别是在有丝分裂、基因表达和遗传稳定性方面。
