Lamins at a glance

Ho, Cheng‐Maw; Lammerding, Jan

doi:10.1242/jcs.087288

Cited by 176 publications

(188 citation statements)

References 144 publications

(148 reference statements)

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“…The finding that these processes can occur independently of cell division implies that CDK1 may play important roles in other aspects of nuclear function. There are several disease-related laminopathies, including Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), limb-girdle muscular dystrophy and Hutchinson-Gilford progeria syndrome, most of which profoundly affect non-proliferating cells (reviewed by Ho and Lammerding, 2012). This work suggests that CDK1, and perhaps other regulators of nuclear structure during mitosis, may play an unappreciated role in terminally differentiated cells.…”

Section: Discussionmentioning

confidence: 99%

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

et al. 2014

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Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIβ (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in combination with either activator cyclins A or B, stimulates mitotic entry, in part, by phosphorylating the nuclear lamin proteins leading to the disassembly of the nuclear lamina and subsequent nuclear envelope breakdown. Although most post-mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins. Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus of the phosphonuclear mitotic apparatus is observed, but it is not focused in CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA replication, resulting in an overall reduction of lens epithelial cells, with the remaining cells possessing an abnormally large nucleus. These observations suggest that CDK1-dependent phosphorylations required for the initiation of nuclear membrane disassembly during mitosis are adapted for removal of nuclei during fiber cell differentiation.

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Section: Discussionmentioning

confidence: 99%

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

et al. 2014

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“…In the somatic cells of humans, mice and most vertebrates, the main forms of lamin protein are expressed from three genes: lamin-A and lamin-C are alternatively spliced products of the LMNA gene, and they are collectively referred to as 'A-type' lamins; lamin-B1 and lamin-B2 are encoded by the LMNB1 and LMNB2 genes, respectively, and are known as 'Btype' lamins. The lamins share structural features and, indeed, have some similarity in amino acid sequence, but they differ in their post-translational modification, with B-type lamins permanently appended by a farnesyl group that is cleaved from mature lamin-A (reviewed, for example, by Dechat et al, 2010;Ho and Lammerding, 2012). Like other intermediate filament proteins, such as keratin and vimentin, the lamins form coiledcoil parallel dimers that assemble into higher-order filamentous structures that fulfill important structural roles ).…”

Section: Introductionmentioning

confidence: 99%

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Swift

Discher

2014

Journal of Cell Science

178

158

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How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.

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“…This could be in part due to increased nuclear stiffness in cells with intact lamina and proper signal transduction cascades. In cells lacking lamin A/C, nuclei are more deformed and fragile with decreased nuclear mechanical stiffness as well as impaired activation of mechanosensitive genes (19,39). As a result, they are potentially more susceptible to all levels of shear stress.…”

Section: Discussionmentioning

confidence: 99%

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation

Nayebosadri

2013

American Journal of Physiology-Cell Physiology

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Nayebosadri A, Ji JY. Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation. Am J Physiol Cell Physiol 305: C309 -C322, 2013. First published May 22, 2013; doi:10.1152/ajpcell.00293.2012The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an antiinflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm 2 ) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-B inhibitor alpha (NF-BIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction. glucocorticoid receptor; nuclear lamina; shear stress; dexamethasone; endothelial cells CARDIOVASCULAR DISEASES SUCH as atherosclerosis are the leading cause of death in the United States. The initiation and development of atherosclerosis are typically associated with endothelial dysfunction (20,51). Endothelial cells at the lumen of blood vessels are continuously exposed to both hemodynamic shear stress and cyclic stretch due to blood flow (16). The distinct local hemodynamic profiles influence endothelial behaviors in the vasculature. Atherosclerotic lesions tend to develop at regions of disturbed flow and low shear stress at bifurcation sites and curvatures, while regions with uniform high laminar shear stress are protected (10,48,66). Endothelial responses to shear stress can be categorized as immediate [rapid release of nitric oxide (NO); (49)] as well as short-term

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Lamins at a glance

Cited by 176 publications

References 144 publications

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation

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