A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus.

Görlich, Dirk; Henklein, Peter; Laskey, Ronald A.; Hartmann, Enno

doi:10.1002/j.1460-2075.1996.tb00530.x

Cited by 393 publications

(345 citation statements)

References 34 publications

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“…We also note that the experiment shown in Fig. 3 was performed with Srp1p protein lacking the N-terminal 72 amino acids of Srp1p, which contain the IBB domain required for binding to Kap95p (5,6). This demonstrates that binding of Srp1p to Nup1p and Nup2p does not require the IBB domain.…”

Section: Srp1p Export Defect In ⌬Nup2mentioning

confidence: 72%

“…The NLS is recognized by importin ␣/Srp1p, which forms a heterodimeric complex with importin ␤/Kap95p. By virtue of its interaction with importin ␤, importin ␣ and its associated NLS-containing protein are carried through the NPC into the nucleus (5,6). Binding of the GTPbound form of the small GTPase Ran to importin ␤ causes dissociation of the import complex in the nucleus (7,8).…”

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confidence: 99%

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The Yeast Nucleoporin Nup2p Is Involved in Nuclear Export of Importin α/Srp1p

Booth

Belanger

Sannella

et al. 1999

Journal of Biological Chemistry

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The importin ␣⅐␤ heterodimer mediates nuclear import of proteins containing classical nuclear localization signals. After carrying its cargo into the nucleus, the importin dimer dissociates, and Srp1p (the yeast importin ␣ subunit) is recycled to the cytoplasm in a complex with Cse1p and RanGTP. Nup2p is a yeast FXFG nucleoporin that contains a Ran-binding domain. We find that export of Srp1p from the nucleus is impaired in ⌬nup2 mutants. Also, Srp1p fusion proteins accumulate at the nuclear rim in wild-type cells but accumulate in the nuclear interior in ⌬nup2 cells. A deletion of NUP2 shows genetic interactions with mutants in SRP1 and PRP20, which encodes the Ran nucleotide exchange factor. Srp1p binds directly to an Nterminal domain of Nup2p. This region of Nup2p is sufficient to allow accumulation of an Srp1p fusion protein at the nuclear rim, but the C-terminal Ran-binding domain of Nup2p is required for efficient Srp1p export.

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Section: Srp1p Export Defect In ⌬Nup2mentioning

confidence: 72%

mentioning

confidence: 99%

The Yeast Nucleoporin Nup2p Is Involved in Nuclear Export of Importin α/Srp1p

Booth

Belanger

Sannella

et al. 1999

Journal of Biological Chemistry

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“…DISCUSSION This study demonstrates that the N-terminal IBB domain of importin ␣ has two essential functions in vivo. This domain is known to bind importin ␤ for targeting of the import complex to the nuclear pore (14,15,46). In addition, previous structural studies demonstrated that the IBB domain contained an NLSlike sequence that could compete directly with NLS binding to importin ␣ through an intramolecular interaction (23,24).…”

Section: Table II Binding Of Importin ␣ Proteins To Nls-cargomentioning

confidence: 99%

The Auto-inhibitory Function of Importin α Is Essentialin Vivo

Harreman

Hodel²,

Fanara³

et al. 2003

Journal of Biological Chemistry

104

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Proteins that contain a classical nuclear localization signal (NLS) are recognized in the cytoplasm by a heterodimeric import receptor composed of importin/ karyopherin ␣ and ␤. The importin ␣ subunit recognizes classical NLS sequences, and the importin ␤ subunit directs the complex to the nuclear pore. Recent work shows that the N-terminal importin ␤ binding (IBB) domain of importin ␣ regulates NLS-cargo binding in the absence of importin ␤ in vitro. To analyze the in vivo functions of the IBB domain, we created a series of mutants in the Saccharomyces cerevisiae importin ␣ protein. These mutants dissect the two functions of the N-terminal IBB domain, importin ␤ binding and autoinhibition. One of these importin ␣ mutations, A3, decreases auto-inhibitory function without impacting binding to importin ␤ or the importin ␣ export receptor, Cse1p. We used this mutant to show that the auto-inhibitory function is essential in vivo and to provide evidence that this auto-inhibitory-defective importin ␣ remains bound to NLS-cargo within the nucleus. We propose a model where the auto-inhibitory activity of importin ␣ is required for NLS-cargo release and the subsequent Cse1p-dependent recycling of importin ␣ to the cytoplasm.In eukaryotes, the nuclear envelope provides an essential barrier that separates the nuclear genome from the intermediary metabolism, signaling systems, and translation machinery of the cytoplasm. Selective bi-directional transport of macromolecules across this nuclear envelope regulates critical cellular processes such as gene expression (1, 2). All nucleocytoplasmic transport of macromolecules occurs through large proteinaceous structures, called nuclear pore complexes (NPC), 1 that perforate the nuclear envelope (3, 4). These macromolecular cargoes are specifically targeted to and transported through NPCs by a family of soluble nuclear transport receptors (5, 6).The small GTPase, Ran, governs the interactions between the nuclear transport receptors and macromolecular cargoes (5, 7). Import receptors bind cargo in the absence of RanGTP, whereas export receptors bind cargo in a trimeric complex with RanGTP (5,8). This mode of regulation requires an asymmetric distribution of RanGTP, with more RanGTP in the nucleus than in the cytoplasm. To achieve this asymmetry, the Ran regulatory proteins are compartmentalized with the GTPase activating protein (RanGAP), which generates RanGDP, in the cytoplasm (9) and the guanine nucleotide exchange factor (RCC1), which generates RanGTP, in the nucleus (10).The best-characterized nuclear import process occurs via receptor recognition of a classical nuclear localization signal (NLS). This classical NLS is typified by a cluster of basic amino acids (monopartite) or two clusters of basic amino acids separated by a 10 -12 amino acid linker (bipartite) (11, 12). A heterodimeric import receptor, composed of importins ␣ and ␤ (also known as karyopherin ␣ and ␤), mediates the nuclear import of proteins that contain a classical NLS (13-15). Over the last several years many...

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“…A fusion protein consisting of this peptide and a reporter was imported into the nucleus independently of NRcz. Unlike NRct, this fusion protein was not exported from the nucleus [19,36]. Thus translocation through the NPC is mediated only by NR[3.…”

Section: Nls-reeeptor (Nr)mentioning

confidence: 99%

“…Thus translocation through the NPC is mediated only by NR[3. Mammalian NRct was observed both in the cytoplasm and in the nucleus [19,30,36]. Yeast NRct was localized to the nucleus, or the NE, or the cytoplasm [21,22,[37][38][39].…”

Section: Nls-reeeptor (Nr)mentioning

confidence: 99%

Protein import into the nucleus

Schlenstedt

1996

FEBS Letters

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The transport of proteins from the cytoplasm into the nucleus is a multistep process. The nuclear localization sequence (NLS) of a transport substrate associates with the heterodimeric NLS-receptor which binds to a subset of proteins of the nuclear pore complex (NPC). Translocation through the NPC is energydependent and requires the small GTPase Ran. Proteins that interact with Ran in either the GDP-bound or the GTP-bound state coordinate transfer through the NPC. Lastly, the NLSreeeptorlsubstrate complex and Ran reach the nuclear side of the NPC where the complex disassembles.

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A 41 amino acid motif in importin-alpha confers binding to importin-beta and hence transit into the nucleus.

Cited by 393 publications

References 34 publications

The Yeast Nucleoporin Nup2p Is Involved in Nuclear Export of Importin α/Srp1p

The Yeast Nucleoporin Nup2p Is Involved in Nuclear Export of Importin α/Srp1p

The Auto-inhibitory Function of Importin α Is Essentialin Vivo

Protein import into the nucleus

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