LINC Complex Proteins in Development and Disease

Horn, Henning F.

doi:10.1016/b978-0-12-397920-9.00004-4

Cited by 57 publications

(58 citation statements)

References 127 publications

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“…This positioning influences diverse processes including cell division, polarity, migration and differentiation. Disruption of normal nuclear positioning is associated with diseases such as muscular dystrophy, cardiomyopathy and lissencephaly [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

“…From these studies, the linker of nucleoskeleton and cytoskeleton (LINC) complex [4], which spans the inner and outer nuclear membrane, has emerged as a widely employed connection between moving nuclei and the cytoskeleton [3, 5]. The LINC complex is composed of outer nuclear membrane KASH proteins (nesprins in vertebrates) and inner nuclear membrane SUN proteins [4-6].…”

Section: Introductionmentioning

confidence: 99%

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Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning

2017

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Summary Nuclear movement is critical for developmental events, cell polarity and migration and is usually mediated by LINC complexes connecting the nucleus to cytoskeletal elements. Compared to active nuclear movement, relatively little is known about homeostatic positioning of nuclei including whether it is an active process. To explore homeostatic nuclear positioning, we developed a method to displace nuclei in adherent cells using centrifugal force. Nuclei displaced by centrifugation rapidly recentered by mechanisms that depended on cell context. In cell monolayers with wounds oriented orthogonal to the force, nuclei were displaced toward the front and back of the cells on the two sides of the wound. Nuclei recentered from both positions, but at different rates and cytoskeletal linkage mechanisms. Rearward recentering was actomyosin-, nesprin-2G- and SUN2-dependent, whereas forward recentering was microtubule-, dynein-, nesprin-2G- and SUN1-dependent. Nesprin-2G engaged actin through its N-terminus and microtubules through a novel dynein interacting site near its C-terminus. Both activities were necessary to maintain nuclear position in uncentrifuged cells. Thus, even when not moving, nuclei are actively maintained in position by engaging the cytoskeleton through the LINC complex.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning

2017

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“…Mutations in LINC complexes cause several human diseases, including Emery–Dreifuss muscular dystrophy (EDMD; Zhang et al , 2007a; Horn, 2014; Meinke et al , 2014). EDMD and the related dilated cardiomyopathy (DCM) are also caused by mutations in genes encoding lamin A and the INM protein emerin (Crisp et al , 2006; Haque et al , 2006, 2010; Worman, 2011; Ho et al , 2014).…”

Section: Introductionmentioning

confidence: 99%

Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA

Thakar

May

Rogers

et al. 2017

MBoC

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Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1. A constitutively active form of SRF/Mkl1 was not sufficient to induce focal adhesion assembly in cells lacking Sun2, however, suggesting that LINC complexes support RhoA activity through a transcription-independent mechanism. Strikingly, we also find that the inner nuclear membrane protein Sun1 antagonizes Sun2 LINC complexes and inhibits RhoA activation and focal adhesion assembly. Thus different LINC complexes have opposing roles in the transcription-independent control of the actin cytoskeleton through the small GTPase RhoA.

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“…6,10,16 Numerous diseases have been shown to be associated with mutations in LINC complex proteins, typically in structural and mechanical tissues such as muscle. 11,17,19 In ''LINCing defective nuclear-cytoskeletal coupling and DYT1 dystonia'', Saunders and Luxton consider how the pathogenesis of the neurological movement disorder DYT1 dystonia might result from dysfunctional regulation of the LINC complex. DYT1 dystonia is caused by a loss-of-function mutation in the ATPases associated with various cellular activities (AAA+) protein, torsinA, which resides within the shared lumen of the endoplasmic reticulum and nuclear envelope.…”

Section: Nuclear-cytoskeletal Coupling Via the Linc Complex And Nuclementioning

confidence: 99%

A Special Topic on Nuclear Mechanobiology

Dahl

Luxton

2016

Cel. Mol. Bioeng.

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LINC Complex Proteins in Development and Disease

Cited by 57 publications

References 127 publications

Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning

Centrifugal Displacement of Nuclei Reveals Multiple LINC Complex Mechanisms for Homeostatic Nuclear Positioning

Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA

A Special Topic on Nuclear Mechanobiology

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