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| Open AccessRegulation by the RNA-binding protein Unkempt at its effector interface
How RNA-binding proteins (RBPs) regulate gene expression via effectors of RNA processing is unclear. Here, the authors dissect the effector interface of an essential RBP, Unkempt, and investigate its contribution to translational control in cells.
- Kriti Shah
- , Shiyang He
- & Jernej Murn
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Article
| Open AccessNardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer
Polo-like kinase 3 (Plk3) has a tumor suppressive role through the induction of apoptosis, however, the mechanism underlying its activation is unclear. Here, in pancreatic cancer, the authors show that activation of Plk3 is dependent on its cleavage into p41Plk3, by the metalloendopeptidase nardilysin.
- Jie Fu
- , Jianhua Ling
- & Paul J. Chiao
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Article
| Open AccessAn adaptive biomolecular condensation response is conserved across environmentally divergent species
Cells must respond to environmental changes. In three fungal species adapted to different temperatures, cellular responses are conserved yet tuned to each organism’s thermal niche, including the formation of adaptive biomolecular condensates.
- Samantha Keyport Kik
- , Dana Christopher
- & D. Allan Drummond
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Article
| Open AccessKinetic trapping organizes actin filaments within liquid-like protein droplets
Here the authors perform modelling to reveal that the timescale of actin-VASP interactions plays a critical role in actin ring formation and filament length determines droplet deformation in VASP droplets: predictions from the model were tested against VASP GAB mutant.
- Aravind Chandrasekaran
- , Kristin Graham
- & Padmini Rangamani
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Article
| Open AccessSalmonella exploits membrane reservoirs for invasion of host cells
The plasma membrane of eukaryotic cells can fold inwards to create reservoirs that store or release excess membrane. Zhu et al. show that Salmonella-secreted effectors modulate these reservoirs to facilitate host cell invasion.
- Hongxian Zhu
- , Andrew M. Sydor
- & John H. Brumell
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Article
| Open AccessIntegrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons
The health of brain cells is known to depend on functional autophagy, but the details are unclear. Here, the authors perform systematic proteomic profiling of human and mouse neurons, delineating the landscape of autophagy degradation in brain.
- Xiaoting Zhou
- , You-Kyung Lee
- & Zhenyu Yue
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Article
| Open AccessLDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
The mechanisms transporting fatty acids into the cell are not completely understood. Here, the authors discover a selective transporter for a specific class of lipids, and show its role in regulating neutrophil function during myocardial ischemia-reperfusion injury.
- Wenwen Tang
- , Yi Luan
- & Dianqing Wu
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Article
| Open AccessBasal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation
Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. Here, Li et al. reveal a morphological cell expansion wave behaviour that coordinates epithelial flattening and tissue elongation during Drosophila oogenesis.
- Shun Li
- , Zong-Yuan Liu
- & Xiaobo Wang
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Article
| Open Accessp53 promotes revival stem cells in the regenerating intestine after severe radiation injury
The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.
- Clara Morral
- , Arshad Ayyaz
- & David G. Kirsch
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Article
| Open AccessEngineering an artificial catch bond using mechanical anisotropy
Catch bonds are unique protein-protein interactions where the bond lifetime increases under external pulling forces. Here, the authors engineer an artificial catch bond based on a non-catch bonding human gut bacterial adhesion protein complex.
- Zhaowei Liu
- , Haipei Liu
- & Michael A. Nash
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Article
| Open AccessDifferentiation granules, a dynamic regulator of T. brucei development
The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
- Mathieu Cayla
- , Christos Spanos
- & Keith R. Matthews
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Article
| Open AccessHalogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Modulating amyloid protein phase separation and fibrilization may help in addressing neurodegenerative diseases. This study demonstrates that halogen-doped graphene quantum dots can modulate these processes in TDP-43 in both nucleus and cytoplasm.
- Hong Zhang
- , Huazhang Guo
- & Bin Dai
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Article
| Open AccessGadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms
Different gene mutations have been reported as drivers for myeloproliferative neoplasms (MPN). Here, the authors show that Gadd45g insufficiency induces MPN in mouse models and associates with MPN in patients.
- Peiwen Zhang
- , Na You
- & Xiaotong Ma
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Article
| Open AccessCompensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs
How growing organs recover from transient injuries is unclear. Here, authors used mouse models of transient cell death in the limb cartilage to identify cellular and molecular mechanisms (e.g. mTORC1) involved in cartilage repair and catch-up growth.
- Chee Ho H’ng
- , Shanika L. Amarasinghe
- & Alberto Rosello-Diez
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Article
| Open AccessTranslation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations
An emerging therapeutic strategy is to suppress nonsense mutations with engineered suppressor tRNAs. Here, the authors show that the mRNA translation velocity is a key parameter determining the efficacy of suppressor tRNAs.
- Nikhil Bharti
- , Leonardo Santos
- & Zoya Ignatova
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Article
| Open AccessSeeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
- Ihsan Dereli
- , Vladyslav Telychko
- & Attila Tóth
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Article
| Open AccessStatins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1
Endothelial dysfunction has been shown to occur in HFpEF and we know that statins can target endothelial dysfunction by inhibiting miR-133a. Here the authors show that statins improve diastolic dysfunction in HFpEF by increasing the levels of a circRNA which, in turns, binds to miR-133a modulating its downstream targets.
- Bin Li
- , Wen-Wu Bai
- & Shuang-Xi Wang
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Article
| Open AccessEph-ephrin signaling couples endothelial cell sorting and arterial specification
Arteries are vital blood vessels for our body and their growth and patterning are critical for proper blood flow. Here they use a retina model to show that a balance of EphB4 receptor and ephrin-B2 ligand integrate a well-wired molecular network to control arteriovenous patterning and vascular growth.
- Jonas Stewen
- , Kai Kruse
- & Mara E. Pitulescu
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Article
| Open AccessAge-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Neural circuit architecture must be maintained during an animal’s lifetime. Here, the authors show that a protective mechanism combining proteostasis and biomechanics supports the integrity of glial cells to environmental stressors.
- Francesca Coraggio
- , Mahak Bhushan
- & Georgia Rapti
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Article
| Open AccessMesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR
Vasectasia is a newly described, non-angiogenic form of blood vessel formation induced by mesenchymal glioblastoma cells, and driven by endothelial cell responses to extracellular vesicles containing oncogenic EGFR.
- Cristiana Spinelli
- , Lata Adnani
- & Janusz Rak
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Article
| Open AccessCold-induced FOXO1 nuclear transport aids cold survival and tissue storage
How tissues adapt to extreme cold is not well understood. Here, the authors discover a mechanism that promotes FOXO1-mediated cold survival gene transcription at low temperatures, with potential implications for long-term tissue storage for transplantation.
- Xiaomei Zhang
- , Lihao Ge
- & Jingxing Ou
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Article
| Open AccessDbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination
The repair of DNA double strand breaks is strictly controlled during the cell cycle by the CDK kinase. Here the authors identify the DDK kinase as a second major regulator for this cell cycle regulation and elucidate its functional targets.
- Lorenzo Galanti
- , Martina Peritore
- & Boris Pfander
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Article
| Open AccessEndocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation
Growth factors rapidly raise cellular glycolysis. Here, authors unveil a mechanism where RTK/GLUT1-containing endocytic vesicles deliver glucose to glycolytic enzymes near mitochondria without upregulating cell surface glucose transporters.
- Ryouhei Tsutsumi
- , Beatrix Ueberheide
- & Yoshiro Saito
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Article
| Open AccessIntron detention tightly regulates the stemness/differentiation switch in the adult neurogenic niche
mRNAs associated with differentiated cells are already detected in adult neural stem cells. Here the authors show how intron detention prevents their translation, solving conflicts in fate decisions while priming stem cells for timely differentiation.
- Ainara González-Iglesias
- , Aida Arcas
- & M. Angela Nieto
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Article
| Open AccessPARP2 promotes Break Induced Replication-mediated telomere fragility in response to replication stress
Here the authors show that PARP2 drives telomere fragility by orchestrating the Break-induced replication (BIR) pathway. This promotes DNA end resection and DNA synthesis via the regulation of POLD3.
- Daniela Muoio
- , Natalie Laspata
- & Elise Fouquerel
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Article
| Open AccessA negative feedback loop between TET2 and leptin in adipocyte regulates body weight
The epigenetic regulation in adipocytes during obesity remains poorly understood. Here, the authors demonstrate a negative feedback loop between TET2, a DNA demethylation enzyme, and leptin, an adipokine, in adipocytes, unveiling a compensatory mechanism by which the body counteracts the metabolic dysfunction induced by obesity.
- Qin Zeng
- , Jianfeng Song
- & Tuo Deng
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Article
| Open AccessPCSK9 stimulates Syk, PKCδ, and NF-κB, leading to atherosclerosis progression independently of LDL receptor
Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to an increase of LDL cholesterol in blood. Here the authors show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor.
- Dasom Shin
- , Soungchan Kim
- & Hyo-Soo Kim
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Article
| Open AccessEnzymatic conversion of human blood group A kidneys to universal blood group O
ABO blood group compatibility restrictions limit the availability of organs for patients awaiting transplantation. Here, the authors show the rapid enzymatic removal of blood group A antigens from the vasculature of human kidneys using normothermic and hypothermic machine perfusion technologies to make universal blood group O organs for transplantation.
- Serena MacMillan
- , Sarah A. Hosgood
- & Michael L. Nicholson
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Article
| Open AccessMembrane fission via transmembrane contact
While fission of single-membrane systems is well understood, the mechanism helping split double membranes (as in organelle division) is unclear. Here, the authors use experiment and theory to discover double membrane fission pathways, and find that a second membrane actually enables splitting.
- Russell K. W. Spencer
- , Isaac Santos-Pérez
- & Marcus Müller
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Article
| Open AccessAdhesion energy controls lipid binding-mediated endocytosis
Many bacterial toxins and viruses deform membranes prior to entering cells via clathrin independent endocytosis. Here the authors show that multivalent lipid binding by globular particles can exceed a threshold adhesion energy required for membrane deformation and that this is sufficient for internalization.
- Raluca Groza
- , Kita Valerie Schmidt
- & Helge Ewers
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Article
| Open AccessMicrointerfaces in biopolymer-based bicontinuous hydrogels guide rapid 3D cell migration
Extracellular microinterfaces provide cells with migration tracks in vivo. Here, the authors introduce these microtracks into bicontinuous hydrogels to elicit rapid cell migration in 3-dimensional contexts.
- Karen L. Xu
- , Nikolas Di Caprio
- & Jason A. Burdick
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Article
| Open AccessCholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds
Cholesterol lowering medication positively affects anti-cancer immune response, but the underpinning mechanism is not fully known. Here authors show that the effect is mediated by specific cholesterol binding motifs in STING, a key mediator of inflammation, via regulating its trafficking to Golgi.
- Bao-cun Zhang
- , Marlene F. Laursen
- & Martin R. Jakobsen
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Article
| Open AccessMitochondrial H2O2 release does not directly cause damage to chromosomal DNA
Nuclear DNA damage downstream of mitochondrial ROS is often cited to contribute to cancer initiation and aging. However, here the authors show that although H2O2 induces DNA mutations when produced near DNA, it does not when released by mitochondria.
- Daan M. K. van Soest
- , Paulien E. Polderman
- & Tobias B. Dansen
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Article
| Open AccessCasein kinase II promotes piRNA production through direct phosphorylation of USTC component TOFU-4
How the production of piRNA is regulated remains elusive. Here the authors showed that casein kinase II mediated direct phosphorylation of USTC component TOFU-4 promotes piRNA production.
- Gangming Zhang
- , Chunwei Zheng
- & Craig Mello
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Article
| Open AccessPheromone-based communication influences the production of somatic extracellular vesicles in C. elegans
Extracellular vesicles are fundamental in cellular communication. Here, authors show how C. elegans pheromones regulate vesicle production, showcasing the impact of social behaviors on cellular mechanisms.
- Agata Szczepańska
- , Katarzyna Olek
- & Michał Turek
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Article
| Open AccessUncovering structural themes across cilia microtubule inner proteins with implications for human cilia function
The inside surface of microtubules contains so-called microtubule inner proteins, but little is known about their identity. Here the authors use bioinformatics to identify structural motifs within this class of proteins and potential new members.
- Jens S. Andersen
- , Aaran Vijayakumaran
- & Kenneth Bødtker Schou
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Article
| Open AccessAutophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation
A seed consists of an embryo, endosperm, and seed coat. Here the authors show that autophagy plays a crucial role in regulating timely programmed cell death in the innermost seed coat, thereby influencing embryo pattern formation and seed viability.
- Lin-lin Zhao
- , Ru Chen
- & Peng Zhao
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Article
| Open AccessSKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration
Secretory autophagy (SA) plays a crucial role in neuroinflammation-driven neurodegeneration, through SKA2 and FKBP5. SKA2 regulation of SA can inhibit IL-1β release. Its dysfunction leads to neurodegeneration, and is linked to Alzheimer’s disease.
- Jakob Hartmann
- , Thomas Bajaj
- & Nils C. Gassen
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Article
| Open AccessNon-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis
PI3 kinase is known to promote cell migration through its catalytic activity. Here, the authors show that the kinase also induces endocytosis through a non-catalytic pathway that actually decreases migratory speed and persistence, revealing a more subtle regulation of motility.
- Hideaki T. Matsubayashi
- , Jack Mountain
- & Takanari Inoue
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Article
| Open AccessActivation of the insulin receptor by insulin-like growth factor 2
IGF2 has a distinct binding affinity for two insulin receptor (IR) isoforms and mimics insulin’s function. Here, the authors present the activation mechanism of IR by IGF2 and reveal the molecular basis for IGF2’s different affinity for two IR isoforms.
- Weidong An
- , Catherine Hall
- & Eunhee Choi
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Article
| Open AccessMyosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads
Myosin-binding protein C (MyBP-C) resides and interacts with the myosin filaments in striated muscle and regulates contraction via an unclear mechanism. Here, the authors demonstrate that MyBP-C regulates the performance of myosin heads.
- Anthony L. Hessel
- , Nichlas M. Engels
- & Samantha P. Harris
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Article
| Open AccessMolecular basis promoting centriole triplet microtubule assembly
Centrioles are characterized by an atypical triplet microtubule structure. Here, the authors discover that the ciliopathy protein HYLS1 promotes the assembly of triplet microtubules within human centrioles.
- Yutaka Takeda
- , Takumi Chinen
- & Daiju Kitagawa
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Article
| Open AccessSNX8 enables lysosome reformation and reverses lysosomal storage disorder
Lysosomal storage disorders (LSDs) are severe genetic diseases currently without routine therapies. Here, the authors identified that SNX8 participates in lysosome reformation and serves as a potential drug target for new therapies to treat LSDs.
- Xinran Li
- , Cong Xiang
- & Xin-Hua Feng
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Article
| Open AccessDefective mitochondria remodelling in B cells leads to an aged immune response
B cell activation in the germinal centre (GC) is accompanied by metabolic adaptation, but the functions of mitochondria remodelling during this process is unclear. Here the authors find that B cell-specific deficiency of Tfam, a transcription factor modulating mitochondria remodelling, impacts GC responses and induces aged immune features in B cells.
- Marta Iborra-Pernichi
- , Jonathan Ruiz García
- & Nuria Martínez-Martín
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Article
| Open AccessFocal adhesions contain three specialized actin nanoscale layers
Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.
- Reena Kumari
- , Katharina Ven
- & Pekka Lappalainen
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Article
| Open AccessAn evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
Unmet expectations, a previously uncharacterized fly protein, is a SAM sensor for the mTORC1 pathway. Tracing the evolution of Unmet reveals that the pathway uses the GATOR2 complex to capture and repurpose ancestral enzymes as nutrient sensors.
- Grace Y. Liu
- , Patrick Jouandin
- & David M. Sabatini
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Article
| Open AccessThe EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression
Eukaryotic initiation translation factor 3 subunit h (EIF3H) possesses an alternative “moonlighting” function of deubiquitinase, while its role in colorectal carcinogenesis remains to be explored. Here the authors show that EIF3H deubiquitinates and stabilizes HAX1, which enhances RAF-MEK-ERK signaling to promote colorectal tumor growth and metastasis.
- Huilin Jin
- , Xiaoling Huang
- & Mong-Hong Lee
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Article
| Open AccessOsteocyte mitochondria regulate angiogenesis of transcortical vessels
Osteocytes are the key cellular components of cortical bone. Here they show that osteocytes transfer mitochondria to the endothelial cells of transcortical vessels (TCVs), which promotes angiogenesis and increases function of the TCV network.
- Peng Liao
- , Long Chen
- & Junjie Gao
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Article
| Open AccessGAS41 modulates ferroptosis by anchoring NRF2 on chromatin
GAS41 is recognized as a histone reader and oncogene, but the mechanism by which GAS41 contributes to tumorigenesis is not well understood. Here, the authors discover that GAS41 is a ferroptosis repressor that anchors NRF2 to chromatin, promoting tumor growth.
- Zhe Wang
- , Xin Yang
- & Wei Gu
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