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| Open AccessSUN1/2 controls macrophage polarization via modulating nuclear size and stiffness
Stiffness and size of the nucleus may affect the function of specific cell types. Here the authors show that LPS treatment of macrophages affects the nucleus stiffness and size involving nuclear envelope proteins SUN1/2, chromatin accessibility and M1 associated gene expression.
- Shi Jiao
- , Chuanchuan Li
- & Zhaocai Zhou
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| Open AccessNuclear lamina strain states revealed by intermolecular force biosensor
In this work, a nanobody based intermolecular strain sensor was used to follow the mechanical strain in the nuclear lamina. The results indicate that mechanical state of the nuclear lamina is not only affected by the cell contractility, but also chromatin packing.
- Brooke E. Danielsson
- , Bobin George Abraham
- & Teemu O. Ihalainen
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| Open AccessOrthodenticle homeobox 2 is transported to lysosomes by nuclear budding vesicles
Many homeodomain transcription factors are secreted and move to neighboring cells. Here, orthodenticle homeobox 2 is shown to be exported from the nucleus in a nuclear membrane, which buds off to then be degraded or secreted.
- Jun Woo Park
- , Eun Jung Lee
- & Jin Woo Kim
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| Open AccessLamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function
LMNA mutations cause severe heart dysfunction. Here the authors show that Lamin A/C plays a key role in 3D chromatin architecture in naïve pluripotent stem cells, which ensures proper cardiovascular cell fate and function, and shed light on the mechanisms involved in LMNA cardiomyopathies.
- Yinuo Wang
- , Adel Elsherbiny
- & Gergana Dobreva
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| Open AccessPolycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
Here the authors developed ‘Lamina-Inducible Methylation and Hi-C’ (LIMe-Hi-C) to simultaneously measure chromosome conformation, DNA methylation, and nuclear lamina positioning. Application of the method revealed dynamic changes upon PRC2 inhibition and an essential function of H3K27me3 in regulating sub-compartments and lamina association.
- Allison P. Siegenfeld
- , Shelby A. Roseman
- & Brian B. Liau
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| Open AccessNuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time
Ribosomal biogenesis is known to require nuclear to cytoplasmic export, but the precise kinetics remain unclear. Here, the authors use super-resolution confocal microscopy and single molecule tracking to visualize export of single pre-60S particles through nuclear pore complexes.
- Jan Andreas Ruland
- , Annika Marie Krüger
- & Ulrich Kubitscheck
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| Open AccessVCP maintains nuclear size by regulating the DNA damage-associated MDC1–p53–autophagy axis in Drosophila
Cells maintain a constant cytoplasm to nucleus volume ratio, although the role of DNA damage is not well explored. Here, the authors use Drosophila to connect TER94, the fly homolog of VCP, to disruption of DNA damage repair, leading to ubiquitinated Mu2 protein accumulation and enlarged nuclei.
- Ya-Chu Chang
- , Yu-Xiang Peng
- & Tzu-Kang Sang
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| Open AccessNonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina
Mechanical strength of in situ assembled nuclear lamin filaments arranged in a 3D meshwork is unclear. Here, using mechanical, structural and simulation tools, the authors report the hierarchical organization of the lamin meshwork that imparts strength and toughness to lamin filaments at par with silk and Kevlar®
- K. Tanuj Sapra
- , Zhao Qin
- & Ohad Medalia
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| Open AccessATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.
- Gururaj Rao Kidiyoor
- , Qingsen Li
- & Marco Foiani
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| Open AccessLoss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology
Mandibuloacral dysplasias (MADs) are rare progeroid syndromes characterized by nuclear morphological and functional abnormalities. Here the authors report that loss of mitochondrial membrane protein MTX2 causes a progeroid MAD sharing clinical features with lamin-associated progeroid syndromes.
- Sahar Elouej
- , Karim Harhouri
- & Annachiara De Sandre-Giovannoli
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Article
| Open AccessNucleoporin TPR is an integral component of the TREX-2 mRNA export pathway
mRNAs export from the nucleus is thought to be regulated in part by three nucleoporins that comprise the nuclear basket, but whether and how distinct basket nucleoporins interact with the RNA export machinery is unclear. Here, the authors use rapid auxin-mediated degradation of basket nucleoporins Nup153, Nup50, and Tpr, and see that Tpr interacts with the TREX-2 mRNA export complex.
- Vasilisa Aksenova
- , Alexandra Smith
- & Mary Dasso
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| Open AccessRole of the nuclear membrane protein Emerin in front-rear polarity of the nucleus
During cell migration, cells are polarized with distinct front vs. rear regions but whether and how polarity is transmitted to the nucleus is unclear. Here the authors show that frontally-biased endoplasmic reticulum and the nuclear membrane protein Emerin contribute to front-rear nuclear cell polarity.
- Paulina Nastały
- , Divya Purushothaman
- & Paolo Maiuri
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| Open AccessNuclear decoupling is part of a rapid protein-level cellular response to high-intensity mechanical loading
Cells must be robust to the mechanical demands of their environments. Here, Gilbert et al. expose cells to high-intensity strain cycling and use proteomics to identify a protein, SUN2, that behaves as a strain-induced breakpoint that can decouple the nucleoskeleton from the cytoskeleton.
- Hamish T. J. Gilbert
- , Venkatesh Mallikarjun
- & Joe Swift
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| Open AccessThe AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn
Torsins are unusual AAA + ATPases of unknown function that reside in the endoplasmic reticulum of all animals. Here the authors report that TorsinA forms tubular helical filaments with an unusual periodicity and that filamentous TorsinA directly interacts with membranes to form tubular protrusions.
- F. Esra Demircioglu
- , Weili Zheng
- & Thomas U. Schwartz
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| Open AccessRif1 S-acylation mediates DNA double-strand break repair at the inner nuclear membrane
Rif1 is involved in different processes such as telomere homeostasis, DNA replication timing, and DNA double strand break (DSB) repair pathway choice. Here, the authors reveal that Rif1 S-acylation facilitates the accumulation of Rif1 at DSBs, attenuation of DNA end-resection, and DSB repair by non-homologous end-joining.
- Gabriele A. Fontana
- , Daniel Hess
- & Ulrich Rass
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Article
| Open AccessNuclear membrane protein Lem2 regulates nuclear size through membrane flow
Nuclear size scales with cell size, but the underlying mechanisms are unclear. Here, the authors report in fission yeast that the inner nuclear membrane protein Lem2 and the ER membrane protein Lnp1 are barriers to membrane flow and propose that they maintain nuclear size in proportion to cell membrane content.
- Kazunori Kume
- , Helena Cantwell
- & Paul Nurse
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| Open AccessCombined loss of LAP1B and LAP1C results in an early onset multisystemic nuclear envelopathy
Nuclear envelopathies are a group of diseases caused by genetic mutations in essential nuclear envelope genes. Here, the authors report a nuclear envelopathy with a homozygous nonsense variant in TOR1AIP1 which leads to changes in the nuclear morphology including large nuclear-spanning channels in patients’ fibroblasts.
- Boris Fichtman
- , Fadia Zagairy
- & Ronen Spiegel
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| Open AccessNuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis
The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here authors show that nucleoplasmic LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs and constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.
- Kamil Sołtysik
- , Yuki Ohsaki
- & Toyoshi Fujimoto
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| Open AccessNuclear microtubule filaments mediate non-linear directional motion of chromatin and promote DNA repair
Following DNA damage, different processes come to action to aid repair. The authors here find that microtubule filaments within the cell nucleus capture and non-randomly mobilize damaged chromatin to mediate DNA repair.
- Roxanne Oshidari
- , Jonathan Strecker
- & Karim Mekhail
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| Open AccessSTEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap
The perinuclear actin cap determines nuclear morphology but its regulation is currently poorly understood. Here, the authors find that an activator of the Rac1 GTPase, STEF/TIAM2, localises to the nuclear envelope and contributes to perinuclear actin and myosin tension, which in turn regulates the actin cap.
- Anna Woroniuk
- , Andrew Porter
- & Angeliki Malliri
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| Open AccessNuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology
An actin cap protects the morphology of the nucleus during cellular mechanical stress. Here, the authors show that the nuclear lamina protein lamin A/C mediates the formation of the actin cap in response to stress, and model the distribution of forces in the presence and absence of the actin cap.
- Jeong-Ki Kim
- , Arghavan Louhghalam
- & Dong-Hwee Kim
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| Open AccessSingle-point single-molecule FRAP distinguishes inner and outer nuclear membrane protein distribution
Nuclear envelope transmembrane proteins (NETs) can reside in the outer or inner nuclear membrane, but distinguishing which membrane they reside in, and their translocation rate, is technically challenging. Here the authors develop a FRAP-based super-resolution microscopy method to obtain this information for several NETs.
- Krishna C Mudumbi
- , Eric C Schirmer
- & Weidong Yang
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| Open AccessEssential role of the Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope
CDKs play central roles in cell cycle regulation and are normally activated by cyclins. Here the authors show that RingoA induces a cyclin-independent function of CDK2 at meiotic telomeres, which regulates their tethering to the nuclear envelope and proper synapsis of homologous chromosomes.
- Petra Mikolcevic
- , Michitaka Isoda
- & Angel R. Nebreda
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| Open AccessNuclear envelope-associated endosomes deliver surface proteins to the nucleus
Endocytosis typically directs proteins on a recycling route back to the plasma membrane, transport to the Golgi apparatus or delivery to the lysosome. Here Chaumet et al.describe a population of vesicles that can fuse directly with the outer nuclear membrane and deliver cargo into the nuclear envelope, where it can be translocated into the nucleoplasm.
- Alexandre Chaumet
- , Graham D. Wright
- & Frederic Bard
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| Open AccessThe tethering of chromatin to the nuclear envelope supports nuclear mechanics
The mechanical properties of the metazoan nucleus can be influenced by the nuclear lamina. Here, Schreiner et al.show that untethering chromatin from the inner nuclear membrane results in highly deformable, softer nuclei, revealing an important role for chromatin in modulating nuclear mechanics.
- Sarah M. Schreiner
- , Peter K. Koo
- & Megan C. King