Nuclear–Cytoplasmic Transport

Abstract

In eukaryotic cells, the genomic DNA in the nucleus is separated from the translational machinery in the cytoplasm by the nuclear envelope. Transport of macromolecules such as proteins and RNA across this membrane is essential for cellular function and requires active nuclear–cytoplasmic transport systems. These systems consist of soluble transport receptors, which recognise and bind cargo in one compartment, mediate transport through nuclear pore complexes embedded in the nuclear envelope and deliver cargo in the target compartment. Disruption of this highly regulated process results in abnormal cell function and is linked to human disease aetiology. Understanding the contribution of nuclear protein and RNA transport to cellular organisation is one of the major challenges in cell biology. Key Concepts Transport into and out of the nucleus is mediated by nuclear pore complexes (NPCs), which are large proteinaceous channels that perforate the nuclear membrane. Proteins destined for import into the nucleus contain a nuclear localisation signal (NLS) and proteins destined for export from the nucleus contain a nuclear export signal (NES), each of which targets them for transport. Soluble transport receptors called importins and exportins or karyopherins recognise and bind macromolecular cargos and facilitate transport through nuclear pore complexes. The asymmetric distribution of RanGDP in the cytoplasm and RanGTP in the nucleus controls the directionality of nuclear transport. Nuclear protein transport can be regulated through inter‐ or intramolecular occlusion of the NLS or NES, post‐translation modification of the targeting signal, compartmental sequestration of the cargo protein or altering properties of the nuclear transport machinery including receptors and nuclear pores. Many classes of RNA are transported via Ran‐regulated, karyopherin‐dependent pathways. mRNA export is highly coupled to mRNA processing and is mediated by distinct receptors. Mutations in nuclear targeting signals and nuclear transport receptors have been linked to several human diseases.