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| Open AccessThe great escape: a Shigella effector unlocks the septin cage
Shigella, an important human pathogen, can secrete effector proteins to invade host cells and evade mechanisms of cell-autonomous immunity. In a new manuscript published in Nature Communications, Xian et al. report that the Shigella kinase effector OspG promotes the ubiquitination of septin cytoskeletal proteins to evade cage entrapment.
- Ana T. López-Jiménez
- , Gizem Özbaykal Güler
- & Serge Mostowy
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Article
| Open AccessTRIM25 predominately associates with anti-viral stress granules
Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs.
- Zehua Shang
- , Sitao Zhang
- & Da Jia
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Article
| Open AccessThree stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin
Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.
- Keitaro Fukuda
- , Yoshihiro Ito
- & Masayuki Amagai
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Article
| Open AccessIRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis
The endoplasmic reticulum (ER) is a major site of lipid peroxidation during ferroptosis. Here authors show that the ER protein IRE1α determines ferroptosis induction via regulating glutathione synthesis independent of the unfolded protein response.
- Dadi Jiang
- , Youming Guo
- & Albert C. Koong
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Article
| Open AccessNuclear actin structure regulates chromatin accessibility
Intranuclear actin contributes to nuclear structure. Inducing actin remodeling within the nucleus regulates chromatin accessibility, and is associated with phenotypic outcomes in mesenchymal stem cells. As such, dynamic actin remodeling may modulate gene expression.
- Buer Sen
- , Zhihui Xie
- & Janet Rubin
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Article
| Open AccessProteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis
MAPK-driven tumorigenesis is often related to epithelial dedifferentiation but the regulatory mechanism is less clear. Here, the authors show that MAPK activation upregulates USP15 to promote deubiquitylation and stability of TBX3, a transcription factor implicated in thyroid development and differentiation, driving tumorigenesis in a BRAFV600E thyroid tumor model.
- Zhenlei Zhang
- , Yufan Wu
- & Li Zhao
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Article
| Open AccessComparison of intramyocellular lipid metabolism in patients with diabetes and male athletes
Endurance athletes and sedentary type 2 diabetes patients swapped their lifestyle for 8 weeks. Athletes store and utilise saturated fat intensely for performant physical activity, and type 2 diabetes patients reversed their dysmetabolic lipid state after endurance training.
- Alice M. Mezincescu
- , Amelia Rudd
- & Dana Dawson
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Article
| Open AccessDrosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions
Vesicle transport ensures cargo delivery to cellular targets. Here, Soltani et al. show that Drosophila Evi5, a multiple sclerosis risk gene in humans, controls vesicular transport of iron-bound transferrins and physically interacts with ferritin.
- Sattar Soltani
- , Samuel M. Webb
- & Kirst King-Jones
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Article
| Open AccessTranscription stress at telomeres leads to cytosolic DNA release and paracrine senescence
Cellular senescence and the process of transcription are intimately linked, yet the mechanisms involved remain unclear. Here the authors show that a defect in TFIIS leads to telomere dysfunction, genome instability and the release of vesicles that induce senescence to neighboring cells.
- Athanasios Siametis
- , Kalliopi Stratigi
- & George A. Garinis
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Article
| Open AccessDynamin1 long- and short-tail isoforms exploit distinct recruitment and spatial patterns to form endocytic nanoclusters
Dynamins are required at nascent endosomes to promote membrane fission. Here, the authors use super-resolution microscopy to show that dynamin-1 recruitment relies on pre-existing nanoclusters and trapping of molecules laterally diffusing on the plasma membrane.
- Anmin Jiang
- , Kye Kudo
- & Frédéric A. Meunier
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Article
| Open AccessmTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism
How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.
- Tal Levy
- , Kai Voeltzke
- & Gabriel Leprivier
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Article
| Open AccessOxidative photocatalysis on membranes triggers non-canonical pyroptosis
Oxidative damage to intracellular membrane proteins is critical to cells. Here, the authors use a water-oxidizing photocatalyst, generating ∙OH even under hypoxia, to show that membrane-specific protein oxidation triggers pyroptosis via non-canonical inflammasomes.
- Chaiheon Lee
- , Mingyu Park
- & Tae-Hyuk Kwon
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Article
| Open AccessMethylation of ESCRT-III components regulates the timing of cytokinetic abscission
Methylation of CHMP2B regulates abscission timing by modulating ESCRT-III dynamics during cytokinesis. This methylation also plays a role in HIV-1 budding, highlighting the broader significance of ESCRT-III methylation.
- Aurélie Richard
- , Jérémy Berthelet
- & Souhila Medjkane
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Article
| Open AccessMapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth
Human hepatocytes remain hard to grow in vitro. Here, the authors temporally map the early stages of organoid growth initiated from fetal and adult hepatocytes, leveraging this knowledge to design maturation and improved expansion conditions.
- Delilah Hendriks
- , Benedetta Artegiani
- & Hans Clevers
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Article
| Open AccessDynamic microvilli sculpt bristles at nanometric scale
Bristleworms possess dedicated cells that can synthesize highly stereotypical bristles with sub-micrometric precision. Here, Ikeda and colleagues shed light on the underlying dynamics of cellular protrusions, revealing an extension-disassembly cycle that resembles a 3D printer.
- Kyojiro N. Ikeda
- , Ilya Belevich
- & Florian Raible
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Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
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Article
| Open AccessSpatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity
Hepatocytes are central for maintaining metabolic homeostasis during nutritional transitions. Here, we show that the structural remodelling of hepatic organelles is part of hepatocytes’ metabolic plasticity to adapt to cycles of fasting/feeding and this process is zonated in the liver.
- Güneş Parlakgül
- , Song Pang
- & Ana Paula Arruda
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Article
| Open AccessImplication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature
The role of subcellular thermogenesis during neuronal differentiation remains poorly understood. Here, the authors employ methods to monitor local intracellular temperature, and they investigate the effects of non-invasive temperature changes on cell differentiation using neuron-like cells.
- Shunsuke Chuma
- , Kazuyuki Kiyosue
- & Yoshie Harada
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Article
| Open AccessA genetically encoded biosensor to monitor dynamic changes of c-di-GMP with high temporal resolution
The ubiquitous second messenger c-di-GMP regulates many biological processes in bacteria, including cell cycle, motility, virulence and biofilm formation. Here, Kaczmarczyk et al. develop a c-di-GMP biosensor that enables dynamic real-time tracking of c-di-GMP levels in individual living cells.
- Andreas Kaczmarczyk
- , Simon van Vliet
- & Urs Jenal
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Article
| Open AccessA common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma
Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.
- Jamie L. Everman
- , Satria P. Sajuthi
- & Max A. Seibold
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Article
| Open AccessCadmium binding by the F-box domain induces p97-mediated SCF complex disassembly to activate stress response programs
The F-box domain is a conserved structural motif in ubiquitin ligases known only to bind Skp1. Here, the authors show the F-box domain is also an environmental cadmium sensor that changes conformation upon binding to disassemble the active ligase, protecting the cell from cadmium stress.
- Linda Lauinger
- , Anna Andronicos
- & Peter Kaiser
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Article
| Open AccessMeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation
The heterochromatic 'condensates' may not be conserved across mammals. This study highlights the influence of host genome on nuclear architecture and challenges the hypothesis that heterochromatin and MeCP2 undergo phase separation.
- Raphaël Pantier
- , Megan Brown
- & Adrian Bird
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Article
| Open AccessPrecise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states
Multiplexed imaging to study cellular pathways can be hampered by lack of antibody specificity, especially when assessing signal activation. Here, the authors present Precise Emission Canceling Antibodies (PECAbs), which enable high-specificity sequential imaging and the study of signaling pathways.
- Kosuke Tomimatsu
- , Takeru Fujii
- & Yasuyuki Ohkawa
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Article
| Open AccessIdentification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease
The LINE-1 retrotransposon is a target for the development of therapies to treat age-associated disease. Here the AUs describes the characterization of small molecule inhibitors of the endonuclease domain of LINE-1.
- Alexandra M. D’Ordine
- , Gerwald Jogl
- & John M. Sedivy
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Article
| Open AccessAn interphase actin wave promotes mitochondrial content mixing and organelle homeostasis
A mitochondrial actin wave fragments mitochondria. Here, the authors find that the wave produces force that is resisted by mitochondrial tethering, inducing fission, with subsequent fusion promoting mitochondrial content mixing and mitochondrial homeostasis.
- Stephen M. Coscia
- , Andrew S. Moore
- & Erika L. F. Holzbaur
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Article
| Open AccessStructural basis for the intracellular regulation of ferritin degradation
Ferritin, the cellular iron storage complex, binds NCOA4 and is trafficked to the lysosome for degradation and iron release. Here, authors present the cryo-EM structure of the NCOA4-Ferritin complex with biophysical and cellular characterization.
- Fabian Hoelzgen
- , Thuy T. P. Nguyen
- & Gabriel A. Frank
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Article
| Open AccessSleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes
Sleep disorders increase the risk and mortality of heart disease. Here, the authors show that sleep fragmentation results in elevated copper levels in the male mouse heart and exacerbates myocardial ischemia–reperfusion injury with increased myocardial cuproptosis and apoptosis.
- Na Chen
- , Lizhe Guo
- & E. Wang
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Article
| Open AccesstauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data
There is a need to determine circadian time in gene expression datasets. Here, authors built tauFisher, a pipeline that predicts circadian time labels from single transcriptomic samples. tauFisher will be useful for determining body clock time in circadian medicine and for research.
- Junyan Duan
- , Michelle N. Ngo
- & Bogi Andersen
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Article
| Open AccessAllosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea
c-di-AMP is essential for bacterial signaling. Here, the authors identify the GlcNAc-sensing regulator DasR as a c-di-AMP receptor and provide molecular insight into their signaling effect on the developmental and antibiotic biosynthesis control across Actinobacteria.
- Di You
- , Liu-Chang Zhao
- & Bang-Ce Ye
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Article
| Open AccessCardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1
The sodium-calcium exchanger (NCX1) is the primary calcium extrusion mechanism of cardiac myocytes. Here, the authors show that removal of a long questioned allosteric regulation of NCX1 by intracellular sodium alters cardiac excitation-contraction coupling.
- Kyle Scranton
- , Scott John
- & Michela Ottolia
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Article
| Open AccessArabidopsis α-Aurora kinase plays a role in cytokinesis through regulating MAP65-3 association with microtubules at phragmoplast midzone
Arabidopsis α-Aurora kinase regulates plant cytokinesis by phosphorylating the microtubule-associated protein MAP65-3, which controls the dynamic organization of the phragmoplast structure essential for cytokinesis completion.
- Xingguang Deng
- , Yu Xiao
- & Honghui Lin
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Article
| Open AccessDeciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis
Here the authors structurally and mechanistically characterize the assembly of FADD, procaspase-8, and cFLIP through their death-effector domains (DEDs), providing insights into the regulation of apoptotic and necroptotic signalling.
- Chao-Yu Yang
- , Chia-I Lien
- & Su-Chang Lin
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Article
| Open AccessGiant organelle vesicles to uncover intracellular membrane mechanics and plasticity
The biophysical properties of cellular organelles are difficult to study directly. Here, the authors generate and characterize osmotically-expanded giant vesicles of several organelles, which maintain some of their functional properties.
- Alexandre Santinho
- , Maxime Carpentier
- & Abdou Rachid Thiam
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Article
| Open AccessAnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics
Annotation of cell types and quantification of their relative localization in tissues remain challenging. Here, the authors present AnnoSpat (Annotator and Spatial Pattern Finder), a computational tool that can automatically identify cell types and quantify cell-cell proximity relationships.
- Aanchal Mongia
- , Fatema Tuz Zohora
- & Robert B. Faryabi
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Article
| Open AccessHPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics
In this work, the authors unveil a mechanism where the Citron homology domain regulates HPK1’s kinase domain, shedding light on the relationship between HPK1’s structure and function. This enhances our understanding of HPK1, an intracellular target for cancer immunotherapy and provides a direction for immuno-oncology drug discovery.
- Avantika S. Chitre
- , Ping Wu
- & Weiru Wang
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Article
| Open AccessEndogenous clock-mediated regulation of intracellular oxygen dynamics is essential for diazotrophic growth of unicellular cyanobacteria
The authors investigate the circadian clock in a unicellular diazotrophic cyanobacterium. They demonstrate the role of the clock in regulating intracellular oxygen dynamics, a necessity to accommodate nitrogen fixation in an oxygen-producing cell.
- Anindita Bandyopadhyay
- , Annesha Sengupta
- & Himadri B. Pakrasi
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Article
| Open AccessAtypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions
The regulation of meiotic prophase progression varies between males and females. This study reveals the involvement of an atypical heat shock transcription factor HSF5 in gene expression during male meiotic prophase and highlights the involved gene regulatory mechanism.
- Saori Yoshimura
- , Ryuki Shimada
- & Kei-ichiro Ishiguro
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Article
| Open AccessDistinguishing individual photobodies using Oligopaints reveals thermo-sensitive and -insensitive phytochrome B condensation at distinct subnuclear locations
Photobodies form via the condensation of the light and temperature sensor phytochrome B. Here, the authors label photobodies using nuclear landmarks to demonstrate the nonrandom thermos-sensitive and -insensitive seeding of distinct photobodies.
- Juan Du
- , Keunhwa Kim
- & Meng Chen
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Article
| Open AccessStress-shape misalignment in confluent cell layers
When studying nematic ordering of cells in a monolayer, it is commonly assumed that the principal stress and cell shape axes are tightly coupled. Here, the authors measure cell shape and cell-generated contractile stresses and show that cells in monolayers form correlated, dynamic domains in which the stresses are systematically misaligned with the cell bodies.
- Mehrana R. Nejad
- , Liam J. Ruske
- & Julia M. Yeomans
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Article
| Open AccessLoss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer
NEDD8 is a ubiquitin-like protein that governs protein neddylation, previously demonstrated to be essential for cell survival. Here the authors show that NEDD8 loss in breast cancer cells is associated with enhanced immunogenicity and increased sensitivity to PD-1 blockade in preclinical cancer models.
- Irineos Papakyriacou
- , Ginte Kutkaite
- & Yumeng Mao
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Article
| Open AccessRinRK1 enhances NF receptors accumulation in nanodomain-like structures at root-hair tip
RinRK1 interacts with NFR1 and NFR5 through their extracellular domains, facilitating a complex with Flot1. This interaction promotes their localization at root hair tip nanodomains, crucial for mediating the rhizobial infection.
- Ning Zhou
- , Xiaolin Li
- & Fang Xie
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Article
| Open AccessDietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion
Enteroendocrine cells in the gut sense food to regulate feeding behavior. Here, the authors show in Drosophila L-glutamate reduces the frequency of calcium oscillations in enteroendocrine cells and decreases the release of NPF, thereby reducing the activation of a pair of anorexic enteric neurons.
- Junjun Gao
- , Song Zhang
- & Zheng Guo
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Article
| Open AccessNumb positively regulates Hedgehog signaling at the ciliary pocket
The precise regulatory mechanisms controlling ciliary Hedgehog signaling remain incomplete. Here, the authors use ciliary proteomics to reveal that Numb facilitates the endocytosis of the receptor Ptch1 from the ciliary pocket, thereby enabling activation of Hedgehog signaling.
- Xiaoliang Liu
- , Patricia T. Yam
- & Xuecai Ge
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Article
| Open AccessPhotobody formation spatially segregates two opposing phytochrome B signaling actions of PIF5 degradation and stabilization
Photobodies are plant nuclear bodies containing the photoreceptor phytochrome B. Here, the authors reveal that photobody formation segregates opposing phytochrome B-mediated light-signaling actions into two phase-separated subnuclear compartments
- Ruth Jean Ae Kim
- , De Fan
- & Meng Chen
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Article
| Open AccessPersistent TFIIH binding to non-excised DNA damage causes cell and developmental failure
Hereditary nucleotide excision repair deficiencies cause different cancerous and progeroid disorders of which the exact etiology is not understood. This study finds that prolonged binding of DNA repair factor TFIIH to DNA damage contributes to a more severe phenotype caused by DNA repair deficiency.
- Alba Muniesa-Vargas
- , Carlota Davó-Martínez
- & Hannes Lans
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Article
| Open AccessIFT cargo and motors associate sequentially with IFT trains to enter cilia of C. elegans
Intraflagellar transport is essential for the formation and function of cilia. Here, the authors use single-molecule imaging in live C. elegans to show that transport trains are formed by the sequential attachment of proteins before departing into the cilium.
- Aniruddha Mitra
- , Elizaveta Loseva
- & Erwin J. G. Peterman
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Article
| Open AccessTANGO1 inhibitors reduce collagen secretion and limit tissue scarring
Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.
- Ishier Raote
- , Ann-Helen Rosendahl
- & Vivek Malhotra
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Article
| Open AccessTemporal coordination of the transcription factor response to H2O2 stress
H2O2 stress is known to activate a slew of transcription factors that restore redox balance. Here, the authors use live-cell imaging and single-cell analysis to reveal that the transcription factors that are activated and their timing of activation is dose dependent.
- Elizabeth Jose
- , Woody March-Steinman
- & Andrew L. Paek
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Article
| Open AccessPhosphorylation of the F-BAR protein Hof1 drives septin ring splitting in budding yeast
Cytokinesis in budding yeast is accompanied by a major rearrangement of septins into a double ring. Here, authors show that the F-BAR protein Hof1 contributes to septin remodeling upon its phosphorylation and relocalisation from septins to the division site.
- Maritzaida Varela Salgado
- , Ingrid E. Adriaans
- & Simonetta Piatti
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