Transport Between the Cell Nucleus and the Cytoplasm

Abstract

The compartmentation of eukaryotic cells requires all nuclear proteins to be imported from the cytoplasm, whereas, for example, transfer RNAs, messenger RNAs, and ribosomes are made in the nucleus and need to be exported to the cytoplasm. Nuclear import and export proceed through nuclear pore complexes and can occur along a great number of distinct pathways, many of which are mediated by importin beta-related nuclear transport receptors. These receptors shuttle between nucleus and cytoplasm, and they bind transport substrates either directly or via adapter molecules. They all cooperate with the RanGTPase system to regulate the interactions with their cargoes. Another focus of our review is nuclear export of messenger RNA, which apparently largely relies on export mediators distinct from importin beta-related factors. We discuss mechanistic aspects and the energetics of transport receptor function and describe a number of pathways in detail.

Intracellular Dynamics of the Ubiquitin-Proteasome-System

“…The classical concept applies for nuclear import of proteasomes. Thus, we will focus on the key components required for the classical pathway ( Gorlich & Kutay, 1999). …”

“…Ran is a small GTPase, named Gsp1 in yeast. Ran exists in its GTP-bound state in the nucleus and in its GDP-bound state in the cytoplasm due to the actions of the Ran guanine nucleotide exchange factor (RanGEF) and the RanGTPase activating protein (RanGAP) in the nucleo- and cytoplasm, respectively ( Gorlich & Kutay, 1999; Moore & Blobel, 1993). In the nucleus, the cargo-importin αβ complex encounters RanGTP, which results in the release of the cargo ( Rexach & Blobel, 1995).…”

Active nuclear import and cytoplasmic retention of activation-induced deaminase

“…The ~50 kDa AID-GFP is at the upper limit of the nuclear pore cut-off 29,30 . We confirmed that AID could mediate active nuclear import by increasing the size of the fusion protein so as to preclude diffusion.…”

“…We confirmed that AID could mediate active nuclear import by increasing the size of the fusion protein so as to preclude diffusion. Since protein shape may strongly influence the ability to diffuse 30 , we used APOBEC2 (A2) as control. Given the homology with A2 and APOBEC3G [31][32][33] , the predicted three-dimensional structure of AID safely allows us to postulate that the monomers of A2 (25.7 kDa) and AID (23.9 kDa) will have a similar general folding, and therefore shape ( Supplementary Fig.…”

The evolutionarily conserved region of the U snRNA export mediator PHAX is a novel RNA-binding domain that is essential for U snRNA export

“…The existence of the nucleus in eukaryotic cells necessitates efficient mechanisms to exchange macromolecules between the nucleus and the cytoplasm+ Many proteins and RNAs are transported across the nuclear envelope through the nuclear pore complexes (NPCs)+ Identification of importin-b family members as major nucleocytoplasmic transport receptors has greatly enhanced our understanding of nuclear transport mechanisms, and has enabled the development of simple but robust models of import and export processes (reviewed in Cole & Hammel, 1998;Dahlberg & Lund, 1998;Izaurralde & Adam, 1998;Mattaj & Englmeier, 1998;Ohno et al+, 1998;Görlich & Kutay, 1999;Hood & Silver, 1999)+ In these models, an import receptor binds to a cargo and carries it into the nucleus+ The receptor then binds to RanGTP (the nuclear form of Ran), resulting in release of the cargo+ In the case of export, an export receptor binds to a cargo in the nucleus cooperatively with RanGTP, forming a trimeric export complex+ This complex moves to the cytoplasm and disassembles due to GTP hydrolysis triggered by Ran's GTPase activating factors in the cytoplasm+ Export of RNA cargoes usually requires more complex mechanisms+ One example of this is U snRNA export+ Major spliceosomal U snRNAs such as U1, U2, and U5 are transcribed in the nucleus by RNA polymerase II and acquire a monomethylated cap structure+ In metazoa, these U snRNAs are initially exported from the nucleus+ They bind in the cytoplasm to a group of proteins termed the Sm proteins+ Subsequently the cap structure is hypermethylated, and the RNA-protein complexes (snRNPs) are imported back to the nucleus, where they take part in pre-mRNA splicing reactions (Mattaj, 1988;Lührmann et al+, 1990)+ It has been shown that the monomethyl cap structure is the only essential signal for U snRNA export and that the leucine-rich nuclear export signal (NES) receptor CRM1/ Exportin 1 (Xpo1) mediates this RNA export (Hamm & Mattaj, 1990;Jarmolowski et al+, 1994;Fischer et al+, 1995;Fornerod et al+, 1997)+…”