Beyond Lamins: Other Structural Components of the Nucleoskeleton

Zhong, Zhixia; Wilson, Katherine L.; Dahl, Kris Noel

doi:10.1016/s0091-679x(10)98005-9

Cited by 45 publications

(41 citation statements)

References 97 publications

(123 reference statements)

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“…Titin is a humongous molecule consisting primarily of Ig-repeat, FN3-repeat, and PEVK domains that has been found in both the nucleus and associated with the spindle (Mechado and Andrew 2000;Fabian et al 2007a;Qi et al 2004;Zhong et al 2010). In muscles, titin is thought to act as a "molecular spring", lengthening due to unfolding of these domains when stretching forces are applied, but shortening after these domains spontaneously refold when stretching forces are lowered (reviewed in Linke and Grützner 2008).…”

Section: Control Of Spindle Lengthmentioning

confidence: 99%

Do nuclear envelope and intranuclear proteins reorganize during mitosis to form an elastic, hydrogel-like spindle matrix?

et al. 2011

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The idea of a spindle matrix has long been proposed in order to account for poorly understood features of mitosis. However, its molecular nature and structural composition have remained elusive. Here, we propose that the spindle matrix may be constituted by mainly nuclear-derived proteins that reorganize during the cell cycle to form an elastic gel-like matrix. We discuss this hypothesis in the context of recent observations from phylogenetically diverse organisms that nuclear envelope and intranuclear proteins form a highly dynamic and malleable structure that contributes to mitotic spindle function. We suggest that the viscoelastic properties of such a matrix may constrain spindle length while at the same time facilitating microtubule growth and dynamics as well as chromosome movement. A corollary to this hypothesis is that a key determinant of spindle size may be the amount of nuclear proteins available to form the spindle matrix. Such a matrix could also serve as a spatial regulator of spindle assembly checkpoint proteins during open and semi-open mitosis.

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Section: Control Of Spindle Lengthmentioning

confidence: 99%

Do nuclear envelope and intranuclear proteins reorganize during mitosis to form an elastic, hydrogel-like spindle matrix?

et al. 2011

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“…Physical connections to the cytoskeleton through the linker of nucleoskeleton and cytoskeleton (LINC) complex (reviewed in refs. [46][47][48] may also relate to nuclear blebbing as part of the mechanotransduction pathway from the cell exterior to the nucleus (49).…”

Section: Resultsmentioning

confidence: 99%

Mechanical model of blebbing in nuclear lamin meshworks

Funkhouser¹,

Sknepnek²,

Shimi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Much of the structural stability of the nucleus comes from meshworks of intermediate filament proteins known as lamins forming the inner layer of the nuclear envelope called the nuclear lamina. These lamin meshworks additionally play a role in gene expression. Abnormalities in nuclear shape are associated with a variety of pathologies, including some forms of cancer and Hutchinson-Gilford Progeria Syndrome, and often include protruding structures termed nuclear blebs. These nuclear blebs are thought to be related to pathological gene expression; however, little is known about how and why blebs form. We have developed a minimal continuum elastic model of a lamin meshwork that we use to investigate which aspects of the meshwork could be responsible for bleb formation. Mammalian lamin meshworks consist of two types of lamin proteins, A type and B type, and it has been reported that nuclear blebs are enriched in A-type lamins. Our model treats each lamin type separately and thus, can assign them different properties. Nuclear blebs have been reported to be located in regions where the fibers in the lamin meshwork have a greater separation, and we find that this greater separation of fibers is an essential characteristic for generating nuclear blebs. The model produces structures with comparable morphologies and distributions of lamin types as real pathological nuclei. Thus, preventing this opening of the meshwork could be a route to prevent bleb formation, which could be used as a potential therapy for the pathologies associated with nuclear blebs.elasticity | Monte Carlo | simulation T he nuclear lamina is a component of the nuclear envelope, whose major structural element is a mesh of type V intermediate filament proteins called lamins. It is the most interior component of the nuclear envelope, located underneath the inner nuclear membrane. There are four major kinds of lamins, which can be split into two types, A and B types. Lamins A and C are A type and encoded by the same gene, whereas lamins B1 and B2 are B type but coded by different genes. Lamins are present at the periphery of the nucleus, where they form the nuclear lamina, but both A-and B-type lamins are also found throughout the nucleoplasm in a relatively nonstructured form with a much higher mobility compared with those lamins incorporated into the lamina meshworks. It has been reported that the nuclear lamina contributes to the mechanical stability of the nucleus (1-3). Lamins have also been found to interact with chromatin and thus, can affect gene expression and DNA replication (4-6).Changes in the overall 3D shape of the nucleus are indicative of a variety of pathologies. Many of these pathologies are the result of mutations in the genes coding for lamins A/C, termed laminopathies (7-9). Examples of such pathologies include the premature aging disorder Hutchinson-Gilford Progeria Syndrome (progeria), Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and generalized lipodystrophy. Additionally, multiple forms of cancer are associated with ...

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“…Nuclei were prepared in cold hypotonic buffer and obtained after loose dounce homogenizer according to Zhong et al (Zhong et al, 2010). Nuclei were pelleted at 2000 g for 20 minutes at 4°C and fixed in 4% PFA.…”

Section: Cell Culture Transfection and Nuclei Preparationmentioning

confidence: 99%

Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus

et al. 2012

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SUMMARYSperm-head elongation and acrosome formation, which take place during the last stages of spermatogenesis, are essential to produce competent spermatozoa that are able to cross the oocyte zona pellucida and to achieve fertilization. During acrosome biogenesis, acrosome attachment and spreading over the nucleus are still poorly understood and to date no proteins have been described to link the acrosome to the nucleus. We recently demonstrated that a deletion of DPY19L2, a gene coding for an uncharacterized protein, was responsible for a majority of cases of type I globozoospermia, a rare cause of male infertility that is characterized by the exclusive production of round-headed acrosomeless spermatozoa. Here, using Dpy19l2 knockout mice, we describe the cellular function of the Dpy19l2 protein. We demonstrate that the protein is expressed predominantly in spermatids with a very specific localization restricted to the inner nuclear membrane facing the acrosomal vesicle. We show that the absence of Dpy19l2 leads to the destabilization of both the nuclear dense lamina (NDL) and the junction between the acroplaxome and the nuclear envelope. Consequently, the acrosome and the manchette fail to be linked to the nucleus leading to the disruption of vesicular trafficking, failure of sperm nuclear shaping and eventually to the elimination of the unbound acrosomal vesicle. Finally, we show for the first time that Dpy19l3 proteins are also located in the inner nuclear envelope, therefore implying that the Dpy19 proteins constitute a new family of structural transmembrane proteins of the nuclear envelope.KEY WORDS: Dpy19l2, Acrosome biogenesis, Globozoospermia, Nuclear envelope, Nuclear lamina, Spermiogenesis, MouseAbsence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus

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Beyond Lamins: Other Structural Components of the Nucleoskeleton

Cited by 45 publications

References 97 publications

Do nuclear envelope and intranuclear proteins reorganize during mitosis to form an elastic, hydrogel-like spindle matrix?

Do nuclear envelope and intranuclear proteins reorganize during mitosis to form an elastic, hydrogel-like spindle matrix?

Mechanical model of blebbing in nuclear lamin meshworks

Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus

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