Chapter 1 - Fifty Years of Nuclear Pores and Nucleocytoplasmic Transport Studies: Multiple Tools Revealing Complex Rules

Abstract

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.