The importin β/importin 7 heterodimer is a functional nuclear import receptor for histone H1

Jäkel, Stefan; Albig, Werner; Kutay, Ulrike; Bischoff, F. Ralf; Schwamborn, Klaus; Doenecke, Detlef; Görlich, Dirk

doi:10.1093/emboj/18.9.2411

Cited by 238 publications

(269 citation statements)

References 73 publications

(136 reference statements)

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“…As expected, in the presence of retic* nuclear import of L23a was clearly detectable. In conclusion, these data in combination with our previous results (9) suggest that there is only one functional import receptor for histone H1 in eukaryotic cells, namely the Imp␤-Imp7 heterodimer.…”

Section: Resultssupporting

confidence: 86%

“…We found that two ␤-family import receptors, namely Imp␤ and Imp7, play a critical role in the import of H1 histones (9). Each of the two import receptors binds the histone weakly when tested individually, but the binding is strong for the Imp␤-Imp7 heterodimer.…”

Section: Resultsmentioning

confidence: 93%

“…Because of their small size, histones might be expected to enter the nucleus simply by diffusion. But we and others have shown that the histones are transported to the nucleoplasm by an energy-dependent and receptor-mediated process (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 94%

“…Many other proteins such as ribosomal proteins (14), cyclin B (23), and core histones (19,20,24,25) are transported by monomeric import receptors, members of the importin ␤ superfamily. An exception is the nuclear transport of linker histone H1, which depends on a heterodimeric receptor consisting of two members of the importin ␤-family, namely Imp␤ and Imp7 (9). This complex is also a functional import receptor of two ribosomal proteins, namely rpL4 and rpL6 (26).…”

mentioning

confidence: 99%

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The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

Bäuerle¹,

Doenecke²,

Albig³

2002

Journal of Biological Chemistry

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After synthesis in the cytoplasm, H1 histones are imported into the nucleus through an energy-dependent process that can be mediated by an importin ␤-importin 7 (Imp␤-Imp7) heterodimer. H1 histones contain two structurally different types of nuclear localization signals (NLS). The first type of NLS resides within the unstructured C-terminal domain and is rich in basic amino acids. In contrast, the highly conserved central domain of the H1 histone contains comparatively few basic amino acids but also represents a functional NLS. The competence for the nuclear import of this globular domain seems to be based on its secondary structure. Here, we show that the Imp␤-Imp7 heterodimer is the only receptor for H1 import. Furthermore, we identified the import receptors mediating the in vitro transport of different NLS of the H1 histone. Using the digitoninpermeabilized cell import assay we show that Imp␤ is the most efficient import receptor for the globular domain of H1 histones, whereas the heterodimer of Imp␤ and Imp7 is the functional receptor for the entire Cterminal domain. However, short fragments of the Cterminal domain are imported in vitro by at least four different importins, which resembles the import pathway of ribosomal proteins and core histones. In addition, we show that heterodimerization of Imp␤ with Imp7 is absolutely necessary for their proper function as an import receptor for H1 histones. These findings point to a chaperone-like function of the heterodimeric complex in addition to its function as an import receptor. It appears that the Imp␤-Imp7 heterodimer is specialized for NLS consisting of extended basic domains.Histones are the protein component of the fundamental structural unit of eukaryotic chromatin, the nucleosome. The nucleosome is composed of a core particle consisting of a histone octamer with 146 bp of DNA bent around its surface and an approximately 50-bp linker DNA connecting two adjacent core particles. This linker DNA is associated with H1 histones; hence they are termed linker histones (1). The four core histones H2A, H2B, H3, and H4 form the histone octamer. Histones are small, very basic proteins. The linker histone H1 is highly enriched in lysine, H2A and H2B are moderately lysinerich, and H3 and H4 are rich in arginine. The size of core histones varies between 11 kDa (H4) and 15 kDa (H3), whereas the H1 histones have a size of ϳ22 kDa. In mammals the class of H1 histones, the linker histones, comprises seven different subtypes, termed H1.1-H1.5, H1°, and H1t (2). Histones are composed of three domains, the very basic, unstructured C-and N-terminal domains and the hydrophobic, central globular domain, which forms the histone fold motif in the case of the core histones (3) and is involved in histone-histone interactions. During the S phase of the cell cycle, a vast amount of newly synthesized histones has to be imported into the nucleus for the formation of nucleosomes on newly replicated DNA. Thus, histones are among the most abundant substrates for nuclear transport during the...

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 93%

mentioning

confidence: 94%

mentioning

confidence: 99%

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The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

Bäuerle¹,

Doenecke²,

Albig³

2002

Journal of Biological Chemistry

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“…NL1 is strongly homologous to the SV40 NLS but shares little apparent similarity to either histone H1(o) or the BIB domain, previously identified as substrates for importin 7 (Jakel and Gorlich, 1998;Jakel et al, 1999). We tested whether the residues required for import by importin ␣ were also required for the import of GR 407-525 by importin 7.…”

Section: Reconstitution Of Gr Nuclear Import In Vitromentioning

confidence: 99%

Importin 7 and Importin α/Importin β Are Nuclear Import Receptors for the Glucocorticoid Receptor

Freedman

2004

MBoC

192

151

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The vertebrate glucocorticoid receptor (GR) is cytoplasmic without hormone and localizes to the nucleus after hormone binding. GR has two nuclear localization signals (NLS): NL1 is similar in sequence to the SV40 NLS; NL2 is poorly defined, residing in the ligand-binding domain. We found that GR displayed similar hormone-regulated compartmentalization in Saccharomyces cerevisiae and required the Sxm1 nuclear import receptor for NL2-mediated import. Two metazoan homologues of Sxm1, importin 7 and importin 8, bound both NL1 and NL2, whereas importin ␣ selectively bound NL1. In an in vitro nuclear import assay, both importin 7 and the importin ␣-importin ␤ heterodimer could import a GR NL1 fragment. Under these conditions, full-length GR localized to nuclei in the presence but not absence of an unidentified component in cell extracts. Interestingly, importin 7, importin 8, and importin ␣ bound GR even in the absence of hormone; thus, hormonal control of localization is exerted at a step downstream of import receptor binding. INTRODUCTIONTo survive in a complex environment, cells sense external cues and commonly respond by altering gene expression, in part by regulating the intracellular localization and activity of transcriptional regulatory factors. For example, the intracellular localization of the yeast Pho4 and mammalian SREBP factors is altered in response to changes in external phosphate and circulating sterol concentrations, respectively (Kaffman et al., 1998b;Nagoshi et al., 1999). Similarly, changes in blood glucose levels and a wide range of physiological stress signals modulate the circulating level of glucocorticoids, changing the activity and localization of the glucocorticoid receptor (GR). Within minutes of glucocorticoid binding, GR enters the nucleus and activates or represses target gene transcription (Picard and Yamamoto, 1987). However, hormone binding is reversible; after hormone withdrawal, GR locates back to the cytoplasm (t 1/2 ϭ 10 h; Hache et al., 1999).Proteins and RNAs enter and exit the nucleus through the nuclear pore, a 125-MDa complex in the nuclear envelope (Stoffler et al., 1999). Small molecules readily diffuse through the nuclear pore, whereas molecules greater than ϳ40 kDa require import and export machinery for transport (Davis, 1995;Pante and Aebi, 1995). The first nuclear localization sequence (NLS) was identified in the SV40 large T-antigen (Kalderon et al., 1984). Development of an in vitro nuclear import assay facilitated the identification of two proteins that import substrates containing SV40 NLS-like domains. The adapter molecule importin ␣ binds to the NLS of the substrate and the importin ␤ transport receptor, creating a trimeric complex that imports the substrate into the nucleus through the nuclear pore (Strom and Weis, 2001).Based on similarity to importin ␤, a family of nuclear import and export receptors was identified and shown to transport a wide variety of proteins and RNAs into and out of the nucleus. After reaching the nucleoplasm, import receptors bind the...

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Nuclear import and export pathways

Moroianu

1999

J. Cell. Biochem.

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Macromolecules enter or leave the nucleus by using nuclear localization signals (NLS), or nuclear export signals (NES), respectively. Different types of NLS and NES are recognized directly or indirectly via adapters, by transport receptors. All transport receptors identified thus far are members of the same family and share an ability to shuttle between the nucleus and the cytoplasm, and to interact with the small GTPase Ran and with nucleoporins at the nuclear pore complex (NPC). The GTPase Ran regulates the interaction of transport receptors with either cargoes, or adapters, or nucleoporins and is crucial in providing directionality to nuclear import and export. Surprisingly, GTP hydrolysis by Ran is not required for translocation of some receptor/cargo complexes through the NPC. One of the challenges for the future will be to establish the mechanisms of translocation through the NPC of different transport receptors together with their cargoes.

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The importin β/importin 7 heterodimer is a functional nuclear import receptor for histone H1

Cited by 238 publications

References 73 publications

The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

Importin 7 and Importin α/Importin β Are Nuclear Import Receptors for the Glucocorticoid Receptor

Nuclear import and export pathways

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