Key Concepts of Section 13.6

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Key Concepts of Section 13.6

Transport Into and Out of the Nucleus

  • The nuclear envelope contains numerous nuclear pore complexes (NPCs), which are large, complex structures composed of multiple copies of 30 different proteins called nucleoporins (see Figure 13-33). FG-nucleoporins, which contain multiple repeats of a short hydrophobic sequence (FG-repeats), line the central transporter channel and play a role in the transport of all macromolecules through nuclear pores.

  • Transport of macromolecules larger than 40 kDa through nuclear pores requires the assistance of nuclear transport receptors that interact with both the transported molecule and FG-repeats of FG-nucleoporins.

  • Proteins imported into or exported from the nucleus contain a specific amino acid sequence that functions as a nuclear-localization signal (NLS) or a nuclear-export signal (NES). Nucleus-restricted proteins contain an NLS but not an NES, whereas proteins that shuttle between the nucleus and cytoplasm contain both signals.

  • Several different types of NESs and NLSs have been identified. Each type of nuclear-transport signal is thought to interact with a specific nuclear transport receptor belonging to a family of homologous proteins.

  • A cargo protein bearing an NES or NLS translocates through nuclear pores bound to its cognate nuclear transport receptor. The transient interactions between nuclear transport receptors and FG-repeats allow very rapid diffusion of nuclear transport receptor–cargo complexes through the central channel of the NPC, which is filled with a hydrophobic matrix of FG-repeats.

  • The unidirectional nature of protein export and import through nuclear pores results from the participation of Ran, a monomeric G protein that exists in different conformations when bound to GTP or GDP. Localization of the Ran guanine nucleotide exchange factor (Ran-GEF) in the nucleus and of the Ran GTPase-activating protein (Ran-GAP) in the cytoplasm creates a gradient with high concentrations of Ran·GTP in the nucleoplasm and of Ran·GDP in the cytoplasm. The interaction of a cargo complex with Ran·GTP in the nucleoplasm causes dissociation of the complex, releasing the cargo into the nucleoplasm (see Figure 13-36), whereas the assembly of an export cargo complex is stimulated by interaction with Ran·GTP in the nucleoplasm (see Figure 13-37).

  • Most mRNPs are exported from the nucleus by binding to a heterodimeric mRNP exporter in the nucleoplasm that interacts with FG-repeats. The direction of transport (nucleus to cytoplasm) results from the action of an RNA helicase associated with the cytoplasmic filaments of the NPC that removes the heterodimeric mRNP exporter once the transport complex has reached the cytoplasm.