Distinct functional domains in nesprin-1α and nesprin-2β bind directly to emerin and both interactions are disrupted in X-linked Emery–Dreifuss muscular dystrophy

Wheeler, Matthew; Davies, John Dwyfor; Zhang, Qiuping; Emerson, Lindsay J.; Hunt, J. Stephen; Shanahan, Catherine M.; Ellis, Juliet A.

doi:10.1016/j.yexcr.2007.03.025

Cited by 82 publications

(80 citation statements)

References 42 publications

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“…Treatment with both enzymes gave the same results as CIP alone (Fig. 7C, lane 16 versus lane 14), suggesting that CIP effectively dephosphorylated both Tyr and Ser/Thr residues in emerin.…”

Section: Ser-53 Ser-54 and Ser-173 Are Relevant To Emerin O-glcnacymentioning

confidence: 64%

“…Plasmids (pET29b) expressing His-tagged emerin residues 1-220, 1-176, or 1-70 and pGEX plasmids expressing GST-tagged emerin residues 70 -140, 140 -176, or 170 -220 were gifts from J. Ellis (14). Missense mutations in pET29b His-emerin 1-220 and pEGFP-C1 emerin were generated by QuikChange site-directed mutagenesis (Agilent Technologies, Santa Clara, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Emerin binds directly to nucleoskeletal proteins (lamin A, actin, and nuclear myosin 1c) (8 -11) and to proteins that form nuclear envelope-spanning LINC ("links the nucleoskeleton and cytoskeleton") complexes (nesprin-1␣, nesprin-2␤, SUN1, and SUN2) (12)(13)(14). Emerin also influences signaling and transcription by binding to partners such as GCL (15), ␤-catenin (16), and Lmo7, which localizes at cell adhesions (17,18) and focal adhesions and is regulated by p130Cas-dependent focal adhesion signaling (19).…”

mentioning

confidence: 99%

“…Mutations in the emerin gene (EMD) cause X-linked recessive Emery-Dreifuss Muscular Dystrophy (EDMD) and related conditions (34). EDMD is also caused by mutations in five other genes (14,(35)(36)(37)(38), most of which encode proteins that either bind emerin (nesprin-1 (SYNE1), nesprin-2 (SYNE2), and lamin A (LMNA)) or associate with emerin in vivo (LUMA (TMEM43)). Evidence supports multiple disease mechanisms, including overactive MAPK signaling (39) and loss of mechanotransduction signaling at the nuclear envelope (1,40).…”

mentioning

confidence: 99%

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O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

Berk

Maitra

Dawdy

et al. 2013

Journal of Biological Chemistry

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Background: Nuclear membrane protein emerin binding to nuclear intermediate filaments (lamins) and BAF contributes to forming a nuclear "lamina" structure. Results: Emerin is O-GlcNAc-modified at eight sites: two (Ser-53 and Ser-54) influence further O-GlcNAcylation, and one (Ser-173) regulates association with BAF in the chromatin/lamin B "niche." Conclusion: O-GlcNAc transferase, a nutrient-responsive enzyme, regulates emerin. Significance: Emerin hyper-O-GlcNAcylation may contribute to cardiomyopathy and other conditions.

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“…Treatment with both enzymes gave the same results as CIP alone (Fig. 7C, lane 16 versus lane 14), suggesting that CIP effectively dephosphorylated both Tyr and Ser/Thr residues in emerin.…”

Section: Ser-53 Ser-54 and Ser-173 Are Relevant To Emerin O-glcnacymentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

Berk

Maitra

Dawdy

et al. 2013

Journal of Biological Chemistry

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show abstract

“…Many of the major discoveries in this field were first made in C. elegans and Drosophila, and then subsequently found to be conserved in vertebrates. In the current model (see Warren et al 2005, Stewart et al 2007 for detailed reviews), nuclear lamins and other nuclear envelope proteins interact with SUN family proteins located at the inner nuclear membrane (Worman & Gundersen 2006, Ketema et al 2007, Liu et al 2007, Wheeler et al 2007. SUN proteins in turn associate across the luminal space with the KASH domain of nesprins residing on the outer nuclear membrane (Padmakumar et al 2005, Crisp et al 2006.…”

Section: Chromatin and The Nuclear Envelopementioning

confidence: 99%

Experimental techniques for study of chromatin mechanics in intact nuclei and living cells

Verstraeten

Lammerding

2008

Chromosome Res

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While the structure of chromatin and its physical properties have been well studied on isolated chromatin fibres and DNA strands in vitro, its organization and function in the intact interphase nucleus is less clear. Chromatin organization is critical for transcriptional regulation and DNA replication, and mounting evidence suggests that cells respond to changes in the mechanical environment with alterations in nuclear architecture that are accompanied by modifications in gene expression. Since the nucleus forms part of a continuous physical network spanning the extracellular matrix, the cytoskeleton and the nuclear envelope, environmentally mediated forces can be transmitted to the nucleus and induce deformations of the chromatin.Here, we describe a subset of techniques that can be applied to probe nuclear mechanics, ranging from micropipette aspiration to strain experiments on living cells. These experiments probe the physical properties of the nuclear envelope, the nucleoplasm, and the chromatin. We discuss the advantages and disadvantages of each technique and elaborate on their use to examine specific aspects of chromatin. In the end, a combination of these technologies can provide important insights into the delicate relationship between form and function of chromatin organization in the living cell.

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Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development

Randles¹,

Lam²,

Sewry³

et al. 2010

Developmental Dynamics

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Nesprins are a family of nuclear transmembrane proteins anchored via Sun proteins to the nuclear membrane. Analysis of nesprins during human muscle development revealed an increase in nesprin-1-giant during early myogenesis in vitro. During the transition from immature to mature muscle fibres in vivo, nesprin-2 partly replaced nesprin-1 at the nuclear envelope and short nesprin isoforms became dominant. Sun1 and Sun2 proteins remained unchanged during this fibre maturation. In emerin-negative skin fibroblasts, nesprin-2-giant was relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum, while nesprin-1 remained at the nuclear envelope. In emerin-negative keratinocytes lacking nesprin-1, nesprin-2 remained at the nuclear envelope. HeLa cell nuclear envelopes lacked nesprin-1, which was the dominant form in myoblasts, while a novel 130kD nesprin-2 isoform dominated Ntera-2 cells. The results suggest the possibility of isoform-specific and tissue-specific roles for nesprins in nuclear positioning.

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Distinct functional domains in nesprin-1α and nesprin-2β bind directly to emerin and both interactions are disrupted in X-linked Emery–Dreifuss muscular dystrophy

Cited by 82 publications

References 42 publications

O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

O-Linked β-N-Acetylglucosamine (O-GlcNAc) Regulates Emerin Binding to Barrier to Autointegration Factor (BAF) in a Chromatin- and Lamin B-enriched “Niche”

Experimental techniques for study of chromatin mechanics in intact nuclei and living cells

Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development

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