The direction of transport through the nuclear pore can be inverted (original) (raw)
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Molecular and cellular biology, 1999
Proteins to be transported into the nucleus are recognized by members of the importin-karyopherin nuclear transport receptor family. After docking at the nuclear pore complex (NPC), the cargo-receptor complex moves through the aqueous pore channel. Once cargo is released, the importin then moves back through the channel for new rounds of transport. Thus, importin and exportin, another member of this family involved in export, are thought to continuously shuttle between the nuclear interior and the cytoplasm. In order to understand how nuclear transporters traverse the NPC, we constructed functional protein fusions between several members of the yeast importin family, including Pse1p, Sxm1p, Xpo1p, and Kap95p, and the green fluorescent protein (GFP). Complexes containing nuclear transporters were isolated by using highly specific anti-GFP antibodies. Pse1-GFP was studied in the most detail. Pse1-GFP is in a complex with importin-alpha and -beta (Srp1p and Kap95p in yeast cells) that ...
The Mechanism of Nucleocytoplasmic Transport through the Nuclear Pore Complex
Cold Spring Harbor Symposia on Quantitative Biology, 2010
Unlike their prokaryotic ancestors, eukaryotic cells contain numerous membrane-bound organelles that compartmentalize various specialized processes. This evolutionary advancement enabled tighter regulation of cellular functions but meant that cells needed to develop channels to transport proteins, ions, and other substances specifically across their internal and external membranes. Of all of the transport channels in a cell, one stands out from all of the others in terms of the range and size of cargoes that pass through it. This is the NPC, which mediates all transport across the nuclear envelope (NE) (the double-membraned layer that separates the nuclear genetic material from the cytoplasm). Transport through the NPC is rapid and bidirectional, with a large set of diverse cargoes crossing between the nucleus and cytoplasm. Cargoes such as transcription factors, ribosomal proteins, and viral nucleic acids enter the nucleus, whereas, messenger ribonucleoproteins (mRNPs), transfer RNAs (tRNAs), and ribosomal subunits exit. Despite the wide range of molecules that must pass through the NPC, nucleocytoplasmic transport is incredibly selective. Transport can also occur very quickly, up to the order of thousands of events per NPC per second (Ribbeck and Gorlich 2001). Yet the structure of the NPC, discussed below, has been found to be surprisingly simple. How this simple structure might mediate this rapid yet selective transport of such a variety of cargoes remains the main question in the field and is the major topic of this chapter. SOLUBLE PHASE OF TRANSPORT Karyopherin-Mediated Transport Numerous lines of evidence have shown that only proteins that can specifically bind to the family of nuclear pore proteins called FG nups are able to efficiently and rapidly cross the NPC. Many such FG-binding proteins act as transport factors, carrying non-FG-binding cargoes across the NPC. Karyopherins (Kaps), also known as importins and exportins, are a family of transport factors that carry proteins and protein/RNA complexes as large as 2 MDa across the NPC (Dworetzky and Feldherr 1988;
The Molecular Mechanism of Transport of Macromolecules Through Nuclear Pore Complexes
Traffic, 2000
Trafficking of macromolecules between nuclear and cytoplasmic compartments takes place through the nuclear pore complexes (NPCs) of the nuclear envelope. Nuclear trafficking involves a complex series of interactions between cargo, soluble transport factors (carriers) and nuclear pore proteins (nucleoporins) that are orchestrated by the Ras-family GTPase Ran. The primary role of Ran is probably to establish directionality and to sort molecules to be transported by controlling the interaction between carriers and cargoes, so that they bind in one compartment but dissociate in the other. Translocation of carriers and cargo-carrier complexes through NPCs requires interactions between the carriers and nucleoporins that contain distinctive tandem sequence repeats based on cores rich in glycine and phenylalanine residues that are separated by hydrophilic linkers. Much recent work has focused on these interactions and, in particular, their specificity, regulation and function. Evidence is accumulating that carriers move through the NPC by distinct but overlapping routes using specific subsets of nucleoporins.
Dynamic localization of the nuclear import receptor and its interactions with transport factors
The Journal of Cell Biology, 1996
Characterization of the interactions between soluble factors required for nuclear transport is key to understanding the process of nuclear trafficking. Using a synthetic lethal screen with the rnal-1 strain, we have identified a genetic interaction between Rnalp, a GTPase activating protein required for nuclear transport, and yeast importin-[3, a component of the nuclear localization signal receptor. By the use of fusion proteins, we demonstrate that Rnalp physically interacts with importin-~. Mutants in importin-~ exhibit in vivo nuclear protein import defects, and importin-[3 localizes to the nuclear envelope along with other proteins associated with the nuclear pore complex. In addition, we present evidence that importin-ot, but not importin-13, mislocalizes to the nucleus in cells where the GTPase Ran is likely to be in the GDP-bound state. We suggest a model of nuclear transport in which Ran-mediated hydrolysis of GTP is necessary for the import of importin-a and the nuclear localization signal-bearing substrate into the nucleus, while exchange of GDP for GTP on Ran is required for the export of both mRNA and importin-a from the nucleus.
Nuclear Pore Complex The Mechanism of Nucleocytoplasmic Transport through the
2011
The nuclear pore complex (NPC) mediates all transport between the nucleus and cytoplasm. Passage through the NPC is highly selective, yet the same channel must allow rapid specific transport of a wide range of cargoes. This chapter focuses mainly on the phenylalanine-glycine (FG) nucleoporins (nups), proteins carrying natively unfolded regions that are thought to form the selectively permeable barrier within the NPC. The physical properties of the FG nup barrier remain unclear. The high selectivity and rapidity of transport observed in vivo may be explained, in part, by competition for binding and space between transport factors and nontransported proteins. Future studies of FG nups will therefore also examine their interactions between FG nups and other proteins in their surroundings.
Importin-beta-like nuclear transport receptors
Genome biology, 2001
In recent years, our understanding of macromolecular transport processes across the nuclear envelope has grown dramatically, and a large number of soluble transport receptors mediating either nuclear import or nuclear export have been identified. Most of these receptors belong to one large family of proteins, all of which share homology with the protein import receptor importin beta (also named karyopherin beta). Members of this family have been classified as importins or exportins on the basis of the direction they carry their cargo. To date, the family includes 14 members in the yeast Saccharomyces cerevisiae and at least 22 members in humans. Importins and exportins are regulated by the small GTPase Ran, which is thought to be highly enriched in the nucleus in its GTP-bound form. Importins recognize their substrates in the cytoplasm and transport them through nuclear pores into the nucleus. In the nucleoplasm, RanGTP binds to importins, inducing the release of import cargoes. In ...
The nuclear pore complex and nuclear transport
Cold Spring Harbor perspectives in biology, 2010
Internal membrane bound structures sequester all genetic material in eukaryotic cells. The most prominent of these structures is the nucleus, which is bounded by a double membrane termed the nuclear envelope (NE). Though this NE separates the nucleoplasm and genetic material within the nucleus from the surrounding cytoplasm, it is studded throughout with portals called nuclear pore complexes (NPCs). The NPC is a highly selective, bidirectional transporter for a tremendous range of protein and ribonucleoprotein cargoes. All the while the NPC must prevent the passage of nonspecific macromolecules, yet allow the free diffusion of water, sugars, and ions. These many types of nuclear transport are regulated at multiple stages, and the NPC carries binding sites for many of the proteins that modulate and modify the cargoes as they pass across the NE. Assembly, maintenance, and repair of the NPC must somehow occur while maintaining the integrity of the NE. Finally, the NPC appears to be an ...
Cell Cycle Regulated Transport Controlled by Alterations in the Nuclear Pore Complex
Cell, 2003
The NPC forms the transport channel across the NE. University of Alberta, Edmonton This complex structure is composed of 03ف proteins Alberta, Canada termed nucleoporins (or nups) (Rout et al., 2000; Cron-T6G 2H7 shaw et al., 2002) that form repetitive substructures or-2 The Institute for Systems Biology ganized with 8-fold symmetry around an axis perpendic-1441 North 34 th Street ular to the NE and 2-fold pseudosymmetry parallel to Seattle, Washington 98103 the NE. Consistent with this organization, most nups can be detected on both the cytoplasmic and nucleoplasmic faces of the NPC. Built upon the symmetrical compo-Summary nents of the NPC are asymmetric fibril structures that extend into the cytoplasm and the nucleoplasm (Rout Eukaryotic cells have developed mechanisms for regand Aitchison, 2001).