Identification of Novel Stress Granule Components That Are Involved in Nuclear Transport

Mahboubi, Hicham; Seganathy, Evangeline; Kong, Dekun; Stochaj, Ursula

doi:10.1371/journal.pone.0068356

Cited by 50 publications

(50 citation statements)

References 59 publications

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“…Chang and Tarn observed that endogenous Transportin‐1 is present in P‐bodies and migrates into SGs when HeLa cells are exposed to various stresses. Importin‐β and its adaptors Importin‐α1, ‐α4 and –α5 [97–99] as well as Transportin‐2B, but not ‐2A (our own unpublished observations), also localize into SGs induced by diverse experimental conditions. This property is nevertheless not shared by all karyopherins.…”

Section: Potential Roles Of Tranportin‐1 and ‐2 Beyond Protein Nucleamentioning

confidence: 79%

Transportin‐1 and Transportin‐2: Protein nuclear import and beyond

2014

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Edited by Ulrike KutayKeywords: Transportin Importins Karyopherins Nuclear import Nucleo-cytoplasmic transport NLS Kap104p Transportin-1 Transportin-2 Karyopherin-b2 hnRNP A1 FUS a b s t r a c t Nearly 20 years after its identification as a new b-karyopherin mediating the nuclear import of the RNA-binding protein hnRNP A1, Transportin-1 is still commonly overlooked in comparison with its best known cousin, Importin-b. Transportin-1 is nonetheless a considerable player in nucleo-cytoplasmic transport. Over the past few years, significant progress has been made in the characterization of the nuclear localization signals (NLSs) that Transportin-1 recognizes, thereby providing the molecular basis of its diversified repertoire of cargoes. The recent discovery that mutations in the Transportin-dependent NLS of FUS cause mislocalization of this protein and result in amyotrophic lateral sclerosis illustrates the importance of Transportin-dependent import for human health. Besides, new functions of Transportin-1 are emerging in processes other than nuclear import. Here, we summarize what is known about Transportin-1 and the related b-karyopherin Transportin-2. Ó 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Basis of protein nucleo-cytoplasmic transportActive nucleo-cytoplasmic transport of proteins is mostly carried out by b-karyopherins, a family of factors functionally divided into importins and exportins. Importins bind to the nuclear localization signal (NLS) of their cargoes in the cytoplasm, either directly or through an adaptor. The importin/cargo complexes cross the nuclear pore complex (NPC) through the interactions of the importin with nucleoporins. In the nucleus, importins are bound by Ran-GTP, which releases the cargo. Importins are then recycled to the cytoplasm in association with Ran-GTP. On the cytoplasmic face of the NPC, Ran hydrolyzes its bound GTP into GDP and dissociates, freeing the importin for a new import cycle (see for example [1] for review). Exportins work in a similar way but in reverse. In the nucleus, exportins cooperatively bind Ran-GTP and a cargo featuring a fitting nuclear export signal (NES). Once the trimeric complexes reach the cytoplasm, they are dissociated and free exportins return to the nucleus to complete the cycle (see for example [2] for review). Thus, while Ran-GTP binding causes importins to release their cargoes, it is required for exportins to bind theirs. Neither importins nor exportins have significant binding affinity for the GDP-bound form of Ran. Therefore, the directionality of the transfers is maintained by mechanisms that ensure that nuclear Ran is bound to GTP and cytoplasmic Ran to GDP. The nuclear part of this task is carried out by the chromatin-associated guanine exchange factor RCC1, which promotes the exchange of GDP for GTP on nuclear Ran. Three factors located on the cytosolic face of the NPC (RanBP1, RanBP2, and RanGAP) collaborate to ensure the hydrolysis of Ran-bound GTP by Ran as soon as it goes ou...

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Section: Potential Roles Of Tranportin‐1 and ‐2 Beyond Protein Nucleamentioning

confidence: 79%

Transportin‐1 and Transportin‐2: Protein nuclear import and beyond

2014

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“…107,108) Furthermore, knocking down importin α (KPNA2) delayed SG formation upon exposure to arsenite, implying its novel regulatory role in the process of SG assembly. 107) …”

Section: Stress Granulesmentioning

confidence: 99%

Importin α: functions as a nuclear transport factor and beyond

Oka

Yoneda

2018

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

104

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Nucleocytoplasmic transport is an essential process in eukaryotes. The molecular mechanisms underlying nuclear transport that involve the nuclear transport receptor, small GTPase Ran, and the nuclear pore complex are highly conserved from yeast to humans. On the other hand, it has become clear that the nuclear transport system diverged during evolution to achieve various physiological functions in multicellular eukaryotes. In this review, we first summarize the molecular mechanisms of nuclear transport and how these were elucidated. Then, we focus on the diverse functions of importin α, which acts not merely an import factor but also as a multi-functional protein contributing to a variety of cellular functions in higher eukaryotes.

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“…Crude cell extracts prepared for HeLa or MCF7 cells were probed side-by-side with primary antibodies and identical concentrations of isotype control IgG (Fig. S1) as previously described [41]. Primary antibodies against CAS, HuR, nucleolin or nucleostemin and fluorescently tagged secondary antibodies were further evaluated by fluorescence microscopy (Fig.…”

Section: Methodsmentioning

confidence: 99%

Identification of Novel Markers That Demarcate the Nucleolus during Severe Stress and Chemotherapeutic Treatment

et al. 2013

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The nucleolus, the ribosomal factory of the cell, has emerged as a key player that regulates many aspects of cell biology. Several thousand proteins associate at least transiently with nucleoli, thereby generating a highly dynamic compartment with a protein profile which is sensitive to changes in cell physiology and pharmacological agents. Powerful tools that reliably demarcate the nucleoli are a prerequisite to measure their composition and activities. Previously, we developed quantitative methods to measure fluorescently labeled molecules in nucleoli. While these tools identify nucleoli under control and mild stress conditions, the accurate detection of nucleolar boundaries under harsh experimental conditions is complicated by the lack of appropriate markers for the nucleolar compartment. Using fluorescence microscopy we have now identified new marker proteins to detect nucleoli upon (a) severe stress and (b) drug treatments that trigger a pronounced reorganization of nucleoli. Our results demonstrate that nucleolin is an ideal marker to delimit nucleoli when cells are exposed to heat or oxidative stress. Furthermore, we show for the first time that cellular apoptosis susceptibility protein (CAS) and human antigen R protein (HuR) are excluded from nucleoli and can be employed to delimit these compartments under severe conditions that redistribute major nucleolar proteins. As proof-of-principle, we used these markers to demarcate nucleoli in cells treated with pharmacological compounds that disrupt the nucleolar organization. Furthermore, to gain new insights into the biology of the nucleolus, we applied our protocols and quantified stress- and drug-induced changes in nucleolar organization and function. Finally, we show that CAS, HuR and nucleolin not only identify nucleoli in optical sections, but are also suitable to demarcate the nucleolar border following 3D reconstruction. Taken together, our studies present novel marker proteins that delimit nucleoli with high confidence under a variety of experimental settings.

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Identification of Novel Stress Granule Components That Are Involved in Nuclear Transport

Cited by 50 publications

References 59 publications

Transportin‐1 and Transportin‐2: Protein nuclear import and beyond

Transportin‐1 and Transportin‐2: Protein nuclear import and beyond

Importin α: functions as a nuclear transport factor and beyond

Identification of Novel Markers That Demarcate the Nucleolus during Severe Stress and Chemotherapeutic Treatment

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