Molecular trafficking across the nuclear pore complex

Gerace, Larry

doi:10.1016/0955-0674(92)90083-o

Cited by 113 publications

(59 citation statements)

References 58 publications

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“…NPCs are closely packed on the surface of the nuclear membrane [27]. Given the diameter of the central transporter region together with the spoke-ring complex of the NPC of approximately 50 to 100 nm [28,29] it is rather difficult to imagine how ion flux through the NPC could be restricted. A possible mechanism through which the cell could gate diffusion processes across the NPC has been suggested by Clapham and coworkers who identified by field emission scanning electron microscopy and atomic force microscopy a central plug in the NPC present in nuclear membrane preparations from Xenopus laevis oocyte [22].…”

Section: Discussionmentioning

confidence: 99%

Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

Eder¹,

Bading²

2007

BMC Neurosci

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BackgroundIn hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types.ResultsUsing laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border.ConclusionThus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

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Section: Discussionmentioning

confidence: 99%

Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

Eder¹,

Bading²

2007

BMC Neurosci

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“…Molecular exchanges between the nucleus and cytoplasm occurring via the nuclear pore complexes (36,37) are fundamentally important for cell growth. The nuclear pore complexes accommodate both passive diffusion of ions and globular proteins of less than 20 kDa (38,39) and active transport of larger macromolecules (36, 37) through a gated channel by sequencedependent (40,41), and energy-dependent mechanisms (42,43).…”

Section: Discussionmentioning

confidence: 99%

Edible Mushroom (Agaricus bisporus) Lectin, Which Reversibly Inhibits Epithelial Cell Proliferation, Blocks Nuclear Localization Sequence-dependent Nuclear Protein Import

Yu¹,

Fernig

White

et al. 1999

Journal of Biological Chemistry

107

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The Gal␤1-3GalNAc␣ (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein-and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 g/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40 -100 g/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

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“…Although it is known that the gated channel of the NPC can expand up to ϳ25 nm in diameter to allow signal-mediated transport (11), this is still considerably smaller than the diameters of many viruses known to replicate in the nucleus. For example, the diameters of SV40, adenovirus, and herpesvirus are 45-50, 60 -90, and 120 -200 nm, respectively.…”

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confidence: 99%

Nuclear Import of Adenovirus DNA in Vitro Involves the Nuclear Protein Import Pathway and hsc70

Saphire

Guan

Schirmer

et al. 2000

Journal of Biological Chemistry

Self Cite

122

102

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Adenovirus, a respiratory virus with a doublestranded DNA genome, replicates in the nuclei of mammalian cells. We have developed a cytosol-dependent in vitro assay utilizing adenovirus nucleocapsids to examine the requirements for adenovirus docking to the nuclear pore complex and for DNA import into the nucleus. Our assay reveals that adenovirus DNA import is blocked by a competitive excess of classical protein nuclear localization sequences and other inhibitors of nuclear protein import and indicates that this process is dependent on hsc70. Previous work revealed that the hexon (coat) protein of adenovirus is the only major protein on the surface of the adenovirus nucleocapsid that docks at the nuclear pore complex. This, together with our finding that in vitro nuclear import of hexon is inhibited by an excess of classical nuclear localization sequences, suggests a role for the hexon protein in adenovirus DNA import. However, recombinant transport factors that are sufficient for hexon import in permeabilized cells do not support DNA import, indicating that there are other as yet unidentified factors required for this process.Proteins are imported into the nucleus through aqueous channels that span the nuclear envelope called nuclear pore complexes (NPCs).1 Whereas ions and molecules less than ϳ20 -40 kDa can diffuse passively through the NPC, larger proteins are transported by saturable pathways that are energy-and signal-dependent. The classical signals that specify nuclear protein import (nuclear localization sequences (NLSs)) are short stretches of amino acids rich in basic residues, although other classes of NLSs have been described recently (1, 2). The transport of NLS-bearing proteins into the nucleus requires the participation of soluble cytosolic factors (3). The advent of a cytosol-dependent in vitro assay for nuclear import (3) has led to the identification of a number of these factors (4), namely importin-␣ (also called the NLS receptor and karyopherin-␣), importin-␤ (also called p97 and karyopherin-␤), Ran (TC4), and NTF2 (also called p10 and pp15). An initial step in the import of proteins containing classical NLSs occurs in the cytoplasm, where the substrate binds to the receptor importin-␣. Subsequently, this complex docks at the cytoplasmic face of the NPC together with importin-␤. The complex is then translocated through a central gated channel of the NPC into the nuclear interior. Movement of the import complex through the NPC requires Ran and NTF2 (5-8), but the precise role of these components is unclear. An additional protein, hsp/hsc70, has been shown to be required for import of some substrates (e.g. the large T-antigen protein (9)), but not of others (e.g. the glucocorticoid receptor (10)).Most viruses that replicate in the nucleus must use the NPC to introduce their genome into the nucleoplasm. Although it is known that the gated channel of the NPC can expand up to ϳ25 nm in diameter to allow signal-mediated transport (11), this is still considerably smaller than the diameters of many ...

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Molecular trafficking across the nuclear pore complex

Cited by 113 publications

References 58 publications

Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

Edible Mushroom (Agaricus bisporus) Lectin, Which Reversibly Inhibits Epithelial Cell Proliferation, Blocks Nuclear Localization Sequence-dependent Nuclear Protein Import

Nuclear Import of Adenovirus DNA in Vitro Involves the Nuclear Protein Import Pathway and hsc70

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