Chain reaction: LINC complexes and nuclear positioning

Burke, Brian

doi:10.12688/f1000research.16877.1

Cited by 25 publications

(26 citation statements)

References 79 publications

(80 reference statements)

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“…Our results show that in addition to Bax-induced MOMP, apoptotic stimuli can cause NPR/SIGRUNB and LINC complex alterations. It is therefore feasible that under conditions where the apoptotic process does not culminate in cell death, Bax-induced NPR/SIGRUNB and nesprin redistribution/degradation may affect cellular process regulated by the LINC complex, such as cell migration and gene expression 23,47,50,51 . Thus, our findings suggest that a new function of Bax may be the modulation of LINC complex-mediated cellular processes is stressed but living cells.…”

Section: Functional Role Of the Bax/nesprin-2 Interaction In Stressedmentioning

confidence: 99%

“…The LINC complex mechanically links the nucleus to the cytoskeleton. It is composed of Klarsicht/ANC-1/ Syne-1 homology (KASH) domain proteins in the outer nuclear membrane and SUN domain proteins in the inner nuclear membrane [22][23][24] . The KASH domain of nesprins projects into the perinuclear space, where it interacts with the SUN domain of SUN proteins.…”

Section: Introductionmentioning

confidence: 99%

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Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins

et al. 2020

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The canonical function of Bcl-2 family proteins is to regulate mitochondrial membrane integrity. In response to apoptotic signals the multi-domain pro-apoptotic proteins Bax and Bak are activated and perforate the mitochondrial outer membrane by a mechanism which is inhibited by their interaction with pro-survival members of the family. However, other studies have shown that Bax and Bak may have additional, non-canonical functions, which include stress-induced nuclear envelope rupture and discharge of nuclear proteins into the cytosol. We show here that the apoptotic stimuli cisplatin and staurosporine induce a Bax/Bak-dependent degradation and subcellular redistribution of nesprin-1 and nesprin-2 but not nesprin-3, of the linker of nucleoskeleton and cytoskeleton (LINC) complex. The degradation and redistribution were caspase-independent and did not occur in Bax/Bak double knockout (DKO) mouse embryo fibroblasts (MEFs). Re-expression of Bax in Bax/Bak DKO MEFs restored stress-induced redistribution of nesprin-2 by a mechanism which requires Bax membrane localization and integrity of the α helices 5/6, and the Bcl-2 homology 3 (BH3) domain. We found that nesprin-2 interacts with Bax in close proximity to perinuclear mitochondria in mouse and human cells. This interaction requires the mitochondrial targeting and N-terminal region but not the BH3 domain of Bax. Our results identify nesprin-2 as a Bax binding partner and also a new function of Bax in impairing the integrity of the LINC complex.

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Section: Functional Role Of the Bax/nesprin-2 Interaction In Stressedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins

et al. 2020

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“…The LINC complex puts in contact the lumen of the NE with the cytoskeleton. This complex is formed by the SUN and KASH proteins, which cross the ONM and the INM [19]. SUN (Sad1, Unc-84) domain proteins are associated with the INM, and KASH (Klarsicht, ANC-1, Syne Homology) domain proteins reside in the ONM [19].…”

Section: Elements Of the Nuclear Envelopementioning

confidence: 99%

Interplay of the nuclear envelope with chromatin in physiology and pathology

Burla

Torre

Maccaroni

et al. 2020

Nucleus

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The nuclear envelope compartmentalizes chromatin in eukaryotic cells. The main nuclear envelope components are lamins that associate with a panoply of factors, including the LEM domain proteins. The nuclear envelope of mammalian cells opens up during cell division. It is reassembled and associated with chromatin at the end of mitosis when telomeres tether to the nuclear periphery. Lamins, LEM domain proteins, and DNA binding factors, as BAF, contribute to the reorganization of chromatin. In this context, an emerging role is that of the ESCRT complex, a machinery operating in multiple membrane assembly pathways, including nuclear envelope reformation. Research in this area is unraveling how, mechanistically, ESCRTs link to nuclear envelope associated factors as LEM domain proteins. Importantly, ESCRTs work also during interphase for repairing nuclear envelope ruptures. Altogether the advances in this field are giving new clues for the interpretation of diseases implicating nuclear envelope fragility, as laminopathies and cancer.

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“…Mechanical loading of chromatin as a consequence of cell migration is dependent on the actin cytoskeleton and LINC complexes [59,60] (Figure 3A). Cytoskeletal contraction induces release of ATP and Ca 2+ , mediating the import of methyltransferases and histone deacetylates, both silencing and activating gene expression [34,35,40].…”

Section: Chromatin Deformation In Response To Cell Motilitymentioning

confidence: 99%

Job Opening for Nucleosome Mechanic: Flexibility Required

Pitman

Melters

Dalal

2020

Cells

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The nucleus has been studied for well over 100 years, and chromatin has been the intense focus of experiments for decades. In this review, we focus on an understudied aspect of chromatin biology, namely the chromatin fiber polymer’s mechanical properties. In recent years, innovative work deploying interdisciplinary approaches including computational modeling, in vitro manipulations of purified and native chromatin have resulted in deep mechanistic insights into how the mechanics of chromatin might contribute to its function. The picture that emerges is one of a nucleus that is shaped as much by external forces pressing down upon it, as internal forces pushing outwards from the chromatin. These properties may have evolved to afford the cell a dynamic and reversible force-induced communication highway which allows rapid coordination between external cues and internal genomic function.

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Chain reaction: LINC complexes and nuclear positioning

Cited by 25 publications

References 79 publications

Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins

Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins

Interplay of the nuclear envelope with chromatin in physiology and pathology

Job Opening for Nucleosome Mechanic: Flexibility Required

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