The inner nuclear membrane protein Lem2 is critical for normal nuclear envelope morphology

Ulbert, Sebastian; Antonin, Wolfram; Platani, Melpomeni; Mattaj, Iain W.

doi:10.1016/j.febslet.2006.10.060

Cited by 62 publications

(67 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1C). In agreement with previously published results involving NET25/Lem2 depletion in HeLa cells (41), the NE was not detectably affected by NET25 depletion in C2C12 cells, as judged by the normal localization of emerin, LAP2␤, and lamins A/C to the NE (data not shown) and normal nuclear morphology (e.g., Fig. 1A).…”

Section: Net25 and Man1 Are Required For Efficient Myoblast Differentsupporting

confidence: 93%

See 1 more Smart Citation

Overlapping Functions of Nuclear Envelope Proteins NET25 (Lem2) and Emerin in Regulation of Extracellular Signal-Regulated Kinase Signaling in Myoblast Differentiation

Huber

Guan

Gerace

2009

Molecular and Cellular Biology

103

118

View full text Add to dashboard Cite

Mutations in certain nuclear envelope (NE) proteins cause muscular dystrophies and other disorders, but the disease mechanisms remain unclear. The nuclear envelope transmembrane protein NET25 (Lem2) is a truncated paralog of MAN1, an NE component linked to bone disorders. NET25 and MAN1 share an ϳ40-residue LEM homology domain with emerin, the protein mutated in X-linked Emery-Dreifuss muscular dystrophy. However, roles for NET25 and MAN1 in myogenesis have not yet been described. Using RNA interference in C2C12 myoblasts, we show for the first time that both NET25 and MAN1 are required for myogenic differentiation. NET25 depletion causes hyperactivation of extracellular signal-regulated kinase 1/2 at the onset of differentiation, and pharmacological inhibition of this transient overactivation rescues myogenesis. In contrast, pharmacological inhibition of both mitogen-activated protein kinase and transforming growth factor ␤ signaling is required to rescue differentiation after MAN1 depletion. Ectopic expression of silencing-resistant NET25 rescues myogenesis after depletion of emerin but not after MAN1 silencing. Thus, NET25 and emerin have at least partially overlapping functions during myogenic differentiation, which are distinct from those of MAN1. Our work supports the hypothesis that deregulation of cell signaling contributes to NE-linked disorders and suggests that mutations in NET25 and MAN1 may cause muscle diseases.The nuclear envelope (NE), which forms the barrier between the nucleus and the cytoplasm, consists of the inner nuclear membrane (INM) and outer nuclear membrane, nuclear pore complexes, and the nuclear lamina. The lamina is a meshwork of intermediate type filament proteins (lamins A/C, B1, and B2) associated with numerous transmembrane proteins of the INM. The transmembrane proteins of the INM include emerin, MAN1, and NET25, the main subjects of this study. The lamina provides a scaffold for the NE and anchoring sites for chromatin and the cytoplasmic cytoskeleton and has been implicated in regulation of gene expression, DNA replication, and cell signaling (reviewed in reference 40).Mutations in genes encoding NE proteins have been causally linked to a host of human diseases (reviewed in reference 43). The most common of these are diseases affecting mesenchymederived tissues, particularly cardiac and skeletal muscle. Autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) (5), limb-girdle muscular dystrophy type 1B (29), and dilated cardiomyopathy (see reference 36 and references therein) are caused by certain mutations in LMNA, the gene encoding lamins A/C. The X-linked form of EDMD results from mutations in EMD, which encodes the lamin A-binding transmembrane protein emerin (4). Although LMNA and EMD mutations account for roughly two-thirds of all reported EDMD cases, the genetic basis for the remaining third remains unknown (19).Muscular dystrophies are diseases that result from increased muscle degeneration and/or impaired muscle regeneration. Satellite cells are the major muscle r...

show abstract

Section: Net25 and Man1 Are Required For Efficient Myoblast Differentsupporting

confidence: 93%

“…siRNA-transfected and control cells were prepared for flow cytometry analysis by ethanol fixation and propidium iodide staining as described previously (41). Data were acquired on a BD FACSCalibur flow cytometer.…”

Section: Methodsmentioning

confidence: 99%

Overlapping Functions of Nuclear Envelope Proteins NET25 (Lem2) and Emerin in Regulation of Extracellular Signal-Regulated Kinase Signaling in Myoblast Differentiation

Huber

Guan

Gerace

2009

Molecular and Cellular Biology

103

118

View full text Add to dashboard Cite

show abstract

“…3A). This is consistent with observations from human cancer cell lines, where knockdown of LEMD2 was reported to alter nuclear morphology (Ulbert et al, 2006). In contrast, the nuclei of emr-1-null mutant embryos were slightly more spherical than control nuclei.…”

Section: Depletion Of Lem-2 Affects Nuclear Envelope Morphology and Psupporting

confidence: 91%

Inner nuclear membrane protein LEM-2 is required for proper nuclear separation and morphology

Morales-Martínez

Dobrzynska

Askjaer

2015

Journal of Cell Science

View full text Add to dashboard Cite

BSTRACTThe inner nuclear membrane proteins emerin and LEMD2 have both overlapping and separate functions in regulation of nuclear organization, gene expression and cell differentiation. We report here that emerin (EMR-1) and LEM domain protein 2 (LEM-2) are expressed in all tissues throughout Caenorhaditis elegans development but their relative distribution differs between cell types. The ratio of EMR-1 to LEM-2 is particularly high in contractile tissues, intermediate in neurons and hypodermis and lowest in intestine and germ line. We find that LEM-2 is recruited earlier than EMR-1 to reforming nuclear envelopes, suggesting the presence of separate mitotic membrane compartments and specific functions of each protein. Concordantly, we observe that nuclei of lem-2 mutant embryos, but not of emr-1 mutants, have reduced nuclear circularity. Finally, we uncover a so-far-unknown role of LEM-2 in nuclear separation and anchoring of microtubule organizing centers.

show abstract

“…125,126 Removal of other inner nuclear membrane lamin-associated proteins such as LEM2 also result in severely altered nuclear morphology, but the mechanism has not been determined. 127 The above findings suggest that there are several, possibly redundant, protein complexes which can connect the cytoskeleton to the nucleoskeleton.…”

Section: Transmission Of Forces To the Nucleus: Cytoskeletal-nuclear mentioning

confidence: 92%

Nuclear Shape, Mechanics, and Mechanotransduction

Dahl

Ribeiro

Lammerding

2008

Circulation Research

606

578

View full text Add to dashboard Cite

Abstract-In eukaryotic cells, the nucleus contains the genome and is the site of transcriptional regulation. The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell and from force generation within the cell. Here, we discuss the effect of intra-and extracellular forces on nuclear shape and structure and how these force-induced changes could be implicated in nuclear mechanotransduction, ie, force-induced changes in cell signaling and gene transcription. We review mechanical studies of the nucleus and nuclear structural proteins, such as lamins. Dramatic changes in nuclear shape, organization, and stiffness are seen in cells where lamin proteins are mutated or absent, as in genetically engineered mice, RNA interference studies, or human disease. We examine the different mechanical pathways from the force-responsive cytoskeleton to the nucleus. We also highlight studies that link changes in nuclear shape with cell function during developmental, physiological, and pathological modifications. Together, these studies suggest that the nucleus itself may play an important role in the response of the cell to force. (Circ Res. 2008;102:1307-1318.)

show abstract

The inner nuclear membrane protein Lem2 is critical for normal nuclear envelope morphology

Cited by 62 publications

References 21 publications

Overlapping Functions of Nuclear Envelope Proteins NET25 (Lem2) and Emerin in Regulation of Extracellular Signal-Regulated Kinase Signaling in Myoblast Differentiation

Overlapping Functions of Nuclear Envelope Proteins NET25 (Lem2) and Emerin in Regulation of Extracellular Signal-Regulated Kinase Signaling in Myoblast Differentiation

Inner nuclear membrane protein LEM-2 is required for proper nuclear separation and morphology

Nuclear Shape, Mechanics, and Mechanotransduction

Contact Info

Product

Resources

About