Compartmentalization of the genome within the nucleus of eukaryotic cells emerged alongside a two-component molecular machinery for selective transport of macromolecules: a static yet conformationally flexible channel formed by the ∼120-MDa nuclear pore complex (NPC), which generates a size-selective diffusion barrier, and a mobile machinery of transport factors and adapters that recognize and ferry macromolecular cargoes across this barrier. Here, we trace the historical development of the nucleocytoplasmic transport field, from early biochemical identification of transport components to contemporary structural and functional insights. We examine how decades of research have illuminated the principles of cargo recognition, the relationship between transport factor structure and function, and the mechanisms that enable unidirectional import and export. The review concludes by highlighting emerging questions about messenger RNA export pathways, mechanosensitive regulation of NPC function, and the role of nucleocytoplasmic transport in health and disease.
Mobbs et al. (2026) studied this question.