Nucleo cytoplasmic trafficking

1. General Information

a. Nuclear Transport Basics

A hallmark of eukaryotes is the compartmentalization of their cells. These compartments like the endoplasmatic reticulum (ER), lysosomes or vesicles are separated from the cytosol by a single membrane, whereas the mitochondria and chloroplasts (in plants) are separated by a double membrane. The strict separation enables the cells to maintain different environmental conditions with respect to pH, salt concentration, metabolites, proteins and also DNA and RNA. One additional compartment, also separated by a double membrane, is the nucleus harboring the DNA. Transcription of DNA and processing of the pre-mRNA to mRNA takes place in the nucleus whereas translation of the mRNA is performed in the cytoplasm.
In general, the compartmentalization offers a multitude of additional control mechanisms for the processes taking place in the organelles. The downside of the spatial separation is the need to transport macromolecules and metabolites across membranes, like proteins and ribonucleic acid (RNA) across the nuclear envelope (Fig.1). This process is essential for cellular function and requires an active nuclear-cytoplasmic transport machinery. This machinery is based on soluble transport receptors, which recognize and bind cargoes in one compartment, mediate their transport through so called nuclear pore complexes (NPCs) which are embedded in the double membrane of the nucleus (Fig. 2) and release the cargoes in the target compartment after traverse. Interestingly, the NPC is an aqueous channel that allows for free diffusion of ions and small metabolites and small proteins. The larger proteins get their diffusion is more and more restricted. NPCs are large macromolecular machines of around 1.2 MDa composed of up to 30 different proteins. They come in multiples of eight, due to the eightfold symmetry of the NPC (see also 1d and 2e for more details) and mediate the interaction to the soluble transport receptors.

Fig.1. Exchange of molecules across the nuclear envelope.
mRNA has to be exported into the cytoplasm in order to be translated, tRNA and ribosomes have to be exported as well, whereas regulatory proteins as well as histones and ribosomal proteins have to be imported into the nucleus.

NPEend size400
Fig.2. Nuclear Pore complexes enable the exchange of molecules across the nuclear envelope. The schematic overall structural arrangement and general organization of the NPC is presented. The coloring indicates different classes of the nucleoporins, further described in 1.d.

Further Reading

  • Wing, C.E., Fung, H.Y.J. and Chook, Y.M. (2022). Karyopherin-mediated nucleocytoplasmic transport. (Review). Nat Rev Mol Cell Biol. 2022 May;23(5):307-328. doi: 10.1038/s41580-021-00446-7. [Abstract]

  • Dickmanns, A. , Kehlenbach, RH. and Fahrenkrog B. (2015) Nuclear Pore Complexes and Nucleocytoplasmic Transport: From Structure to Function to Disease. Int Rev Cell Mol Biol. 320:171-233. [Abstract]