Interaction between Emerin and Nuclear Lamins

Sakaki, Masayo; Koike, Hisashi; Takahashi, Nobuhiro; Sasagawa, Noboru; Tomioka, Sadatake; Arahata, Kiichi; Ishiura, Shoichi

doi:10.1093/oxfordjournals.jbchem.a002860

Cited by 134 publications

(90 citation statements)

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“…EDMD is also caused by mutations in the gene encoding emerin, a LEM domain protein (Bione et al, 1994;Manilal et al, 1996;Nagano et al, 1996). Emerin interacts with A-type lamins (Clements et al, 2000;Sakaki et al, 2001) and is mislocalized in many patients with LMNA mutations (Ben-Harush et al, 2009;Muchir et al, 2003;Sullivan et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

The role ofDrosophilaLamin C in muscle function and gene expression

et al. 2010

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SUMMARYThe inner side of the nuclear envelope (NE) is lined with lamins, a meshwork of intermediate filaments that provides structural support for the nucleus and plays roles in many nuclear processes. Lamins, classified as A-or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. In humans, mutations in A-type lamins give rise to diseases that exhibit tissue-specific defects, such as Emery-Dreifuss muscular dystrophy. Drosophila is being used as a model to determine tissue-specific functions of A-type lamins in development, with implications for understanding human disease mechanisms. The GAL4-UAS system was used to express wild-type and mutant forms of Lamin C (the presumed Drosophila A-type lamin), in an otherwise wild-type background. Larval muscle-specific expression of wild type Drosophila Lamin C caused no overt phenotype. By contrast, larval muscle-specific expression of a truncated form of Lamin C lacking the N-terminal head (Lamin C N) caused muscle defects and semi-lethality, with adult 'escapers' possessing malformed legs. The leg defects were due to a lack of larval muscle function and alterations in hormoneregulated gene expression. The consequences of Lamin C association at a gene were tested directly by targeting a Lamin C DNAbinding domain fusion protein upstream of a reporter gene. Association of Lamin C correlated with localization of the reporter gene at the nuclear periphery and gene repression. These data demonstrate connections among the Drosophila A-type lamin, hormone-induced gene expression and muscle function. DEVELOPMENT 3068 lethality when expressed in larval muscle but not in other tissues (Schulze et al., 2009). By contrast, alterations in the rod domain cause abnormal lamin aggregation within the nucleus but not lethality. Collectively, our studies support a role for the N-terminal head and C-terminal globular domain in larval muscle function.To better understand the role of the N-terminal head domain, we generated transgenic flies expressing a mutant form of Lamin C lacking the first 42 amino acids (Lamin C N) (Schulze et al., 2009). This mutant form localizes to the NE and causes semilethality when expressed in muscle but not in non-muscle tissues (Schulze et al., 2009). Here, we demonstrate that lethality is associated with larval body wall muscle defects that include nuclear and cytoplasmic abnormalities. 'Adult escapers' expressing Lamin C N have leg defects that are consistent with a loss of muscle function and disruptions in ecdysone hormone signaling.Collectively, these studies demonstrate a role for the N-terminal head domain of Lamin C in muscle function and gene expression. MATERIALS AND METHODS Drosophila stocks and genetic analysesDrosophila stocks were raised at room temperature on standard sucrose and cornmeal medium (Shaffer et al., 1994). Generation of transgenic stocks expressing wild type and Lamin C N was previously reported (Schulze et al., 2005;Schulze ...

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Section: Introductionmentioning

confidence: 99%

The role ofDrosophilaLamin C in muscle function and gene expression

et al. 2010

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“…Protein fragments can easily be used as bait since they don't have to be incorporated in vivo, and have been applied to describe interactions between the specific domains of the nuclear envelope proteins otefin, lamin A, nesprin. 45,49,50 The benefit of choosing the exact bait composition can further be exploited by choosing domains involved in disease mechanisms, like the 50 amino acid deleted region in progerin, shown in a Y2H screen to interact with the NURD chromatin remodeling complex component Rbbp4. 6 Disadvantages of Y2H assays are the lack of information on protein complex composition, the inability to study posttranslational modifications and the large amount of false positives identified.…”

Section: Novel Interactors Identified By Msmentioning

confidence: 99%

Mapping of protein- and chromatin-interactions at the nuclear lamina

Kubben

Voncken

Misteli³

2010

Nucleus

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“…After blocking with PBS containing 2% BSA and 5% heatinactivated normal goat serum, the sections were incubated with primary antibodies for 2 hours at 37°C. Primary antibodies used in this study are: rabbit anti-phospho-A-type lamin polyclonal antibodies at 1:50; mouse anti-human merosin (M-chain) monoclonal antibody (5H2) (Chemicon International, Temecula, CA) at 1:400; rabbit anti-lamin A polyclonal antibody (Sakaki et al, 2001) at 1:400; mouse anti-Pax7 monoclonal antibody (Developmental Studies Hybridoma Bank, Iowa City, IA) at 1:300. Sections were incubated with anti-rabbit IgG antibody conjugated with AlexaFluor-488 and anti-mouse IgG antibody conjugated with Alexa-Fluor-568 (Invitrogen, Carlsbad, CA) at 1:500 for 45 minutes at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%