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| Open AccessO-GlcNAcylation regulates neurofilament-light assembly and function and is perturbed by Charcot-Marie-Tooth disease mutations
The neurofilament cytoskeleton is critical for axon function and can be dysregulated in disease. Here, the authors show that intracellular glycosylation regulates a key neurofilament protein.
- Duc T. Huynh
- , Kalina N. Tsolova
- & Michael Boyce
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Article
| Open AccessSalmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection
Vimentin is an intermediate filament protein responsible for maintaining cell shape. Here, the authors characterise the role of the Salmonella effector SopB on the vimentin network and its contribution to infection.
- Shuangshuang Zhao
- , Qiuping Xu
- & Yaming Jiu
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Article
| Open AccessNestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing
The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.
- Senyu Yao
- , Xiaoyue Wei
- & Jiancheng Wang
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Article
| Open AccessQuantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility
PIAS1 is an E3 SUMO ligase involved in various cellular processes. Here, the authors use quantitative proteomics to identify potential PIAS1 substrates in human cells and elucidate the biological consequences of PIAS1-mediated SUMOylation of vimentin.
- Chongyang Li
- , Francis P. McManus
- & Pierre Thibault
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Article
| Open AccessNestin regulates cellular redox homeostasis in lung cancer through the Keap1–Nrf2 feedback loop
Loss of Nestin sensitizes non-small cell lung carcinoma (NSCLC) to oxidative stress. Here, the authors report a feedback loop between Nestin and Nrf2 wherein Nestin competes with Nrf2 for Keap1 binding, preventing Nrf2 degradation, and show the Nestin–Keap1–Nrf2 axis to regulate redox homeostasis in NSCLC.
- Jiancheng Wang
- , Qiying Lu
- & Andy Peng Xiang
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Article
| Open AccessVimentin filaments interact with the actin cortex in mitosis allowing normal cell division
The intermediate filament vimentin reorganizes during mitosis, but its molecular regulation and impact on the cell during cell division is unclear. Here, the authors show that vimentin filaments redistribute to the cell cortex during mitosis intertwining with and affecting actin organization.
- Sofia Duarte
- , Álvaro Viedma-Poyatos
- & Dolores Pérez-Sala
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Article
| 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 AccessNuclear Nestin deficiency drives tumor senescence via lamin A/C-dependent nuclear deformation
Nestin can be localised in the nucleus of cancer cells, but its nuclear role in tumorigenesis is unclear. Here, the authors show that nuclear Nestin prevents senescence in tumor cells by stabilising lamin A/C from proteasomal degradation to maintain nuclear integrity.
- Yanan Zhang
- , Jiancheng Wang
- & Andy Peng Xiang
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Article
| Open Accessp63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response
Mutations in the gene encoding iRHOM2 are associated with hyperproliferative epidermal disorders. Here, the authors show that iRHOM2 is a target gene of p63, that together they regulate inflammation, cell survival and response to oxidative stress, and inhibition of p63-iRHOM2 signalling with an antioxidant reduces epidermal inflammation.
- Paola Arcidiacono
- , Catherine M. Webb
- & Anissa Chikh
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Article
| Open AccessRhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Keratin 16 is an epithelial protein highly expressed at pressure bearing sites and during wound healing and cancer. Here the authors show that K16 interacts with the inactive protease Rhbdf2, associated with Tylosis with oesophageal cancer, and that this interaction drives increased keratinocyte proliferation.
- Thiviyani Maruthappu
- , Anissa Chikh
- & David P. Kelsell
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Article
| Open AccessMechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin
Plakin proteins link cell junctions to cytoskeletal frameworks, and their disruption within epithelial and cardiac muscle cells cause skin blistering diseases and cardiomyopathies. Here the authors use structural biology approaches to reveal the mechanism that allows plakins to recognize intermediate filaments within the cytoskeleton.
- Claudia Fogl
- , Fiyaz Mohammed
- & Martyn Chidgey
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Article
| Open AccessVimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding
Vimentin is an intermediate filament protein that is targeted by oxidative modification at its single cysteine residue, C328. Here Pérez-Sala et al. reveal a role for this cysteine in vimentin organization and function, and uncover a protective role for zinc binding in filament stability.
- Dolores Pérez-Sala
- , Clara L. Oeste
- & F. Javier Cañada