Featured
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Article
| Open AccessStabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells
Post-translational modifications including protein sumoylation is under specific regulation in glioma stem cells (GSCs). Here, the authors show that Pin1 is deubiquitinated and stabilized by USP34, which in turn promotes isomerization of Ubc9, leading to SUMO1-modified global hypersumoylation to maintain the tumorigenic capacity of GSCs.
- Qiuhong Zhu
- , Panpan Liang
- & Wenchao Zhou
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Article
| Open AccessInnate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis
The evolutionally conserved Hippo pathway regulates essential developmental, homeostatic and regenerative processes, and is involved in the host defense against pathogens. Here authors show that in Drosophila Melanogaster and mammalian cells, innate immune stimuli activate Hippo via a pathway emanating from the Tak1 kinase and cascading down to Hippo via STRIPAK-Tao-Hpo signaling.
- Yinan Yang
- , Huijing Zhou
- & Bo Liu
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Article
| Open AccessMic19 depletion impairs endoplasmic reticulum-mitochondrial contacts and mitochondrial lipid metabolism and triggers liver disease
The molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, authors uncover a role for the EMC2- SLC25A46-Mic19 axis in mitochondrial lipid metabolism and liver disease
- Jun Dong
- , Li Chen
- & He He
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Article
| Open AccessMCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation
B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.
- Wenna Chi
- , Na Kang
- & Ligong Chen
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Article
| Open AccessEpithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling
IL-17 mediated inflammation in the lung is mediated by different effector molecules. Here the authors show that the epigenetic regulator epithelial sirtuin 6 (Sirt6) is associated with lung inflammation in asthma patients and that Sirt6 contributes to promotion of inflammation in mouse asthma models.
- Jingyun Quan
- , Xiaoxia Wen
- & Tianwen Lai
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Article
| Open AccessBACH1 controls hepatic insulin signaling and glucose homeostasis in mice
Hepatic insulin resistance plays a central role in metabolic syndrome. Here, the authors show that transcription factor BACH1 acts as a negative regulator of insulin signaling and that hepatic BACH1 deficiency ameliorates hyperglycemia and insulin resistance in high-fat diet-fed or diabetic mice
- Jiayu Jin
- , Yunquan He
- & Dan Meng
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Article
| Open AccessRedox-enabled electronic interrogation and feedback control of hierarchical and networked biological systems
With redox-linked synthetic biology and electrobiofabrication, electronic information can be transmitted in a bidirectional manner between biology and electronics. Here the authors design an electrogenetic platform that allows real time electronic control of biological functions from proteins and gene circuits to cell consortia.
- Sally Wang
- , Chen-Yu Chen
- & William E. Bentley
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Article
| Open AccessUnique adipose tissue invariant natural killer T cell subpopulations control adipocyte turnover in mice
Invariant natural killer T (iNKT) cells have recently been reported to play a key role in adipose tissue homeostasis. Here, the authors show that adipose tissue iNKT cells mediate immune responses that control adipocyte turnover in mice.
- Sang Mun Han
- , Eun Seo Park
- & Jae Bum Kim
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Article
| Open AccessVWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes
mTORC1 adapts cellular metabolism in response to nutrient signals. Here, the authors identify VWCE as a negative regulator of amino acid-dependent mTORC1 signaling and a potential as a therapeutic target in prostate cancer treatments.
- Tianyu Zhao
- , Yuanyuan Guan
- & Ying Liu
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Article
| Open AccessForce transmission by retrograde actin flow-induced dynamic molecular stretching of Talin
Focal adhesion proteins transmit intracellular forces to the extracellular matrix (ECM). Here, the authors show a force transmission by elastic transient clutch of Talin between ECM and constantly flowing F-actin at focal adhesions.
- Sawako Yamashiro
- , David M. Rutkowski
- & Naoki Watanabe
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Article
| Open AccessMtfp1 ablation enhances mitochondrial respiration and protects against hepatic steatosis
Excessive lipid accumulation in hepatocytes causes fatty liver disease and liver failure. Here the authors show that ablation of Mitochondrial Fission Process 1 in hepatocytes in mice protects fatty liver disease and dysfunction caused by high fat diet.
- Cecilia Patitucci
- , Juan Diego Hernández-Camacho
- & Timothy Wai
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Article
| Open AccessAdult stem cell activity in naked mole rats for long-term tissue maintenance
Authors report that long-term intestinal tissue maintenance in naked mole rats is achieved by having an expanded pool of slow-dividing adult stem cells while a higher proportion of differentiated cells confer enhanced function and protection to the intestinal mucosa.
- Shamir Montazid
- , Sheila Bandyopadhyay
- & Shazia Irshad
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Article
| Open AccessMechanical control of neural plate folding by apical domain alteration
Theoretical and experimental observations argue that apical domain heterogeneity in the neural plate is a tug-of-war contest between constricted and elongated cells. This competition likely reflects mechanical forces operating during tissue bending.
- Miho Matsuda
- , Jan Rozman
- & Sergei Y. Sokol
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Article
| Open AccessNEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62.
- Nikolas Furthmann
- , Verian Bader
- & Konstanze F. Winklhofer
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Article
| Open AccessA DARPin promotes faster onset of botulinum neurotoxin A1 action
Botulinum neurotoxins (BoNTs), the causative agents of the disease botulism, are potent biological toxins. Here the authors use Designed Ankyrin Repeat Proteins (DARPins) to probe BoNT structure and function: DARPin-F5 that completely blocks SNAP25 substrate cleavage by BoNT/A1 in vitro was identified.
- Oneda Leka
- , Yufan Wu
- & Richard A. Kammerer
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Article
| Open AccessFunctional-metabolic coupling in distinct renal cell types coordinates organ-wide physiology and delays premature ageing
Spatially resolved metabolism in complex tissues is vital but poorly understood. Here, the authors establish the Drosophila renal system as a paradigm for linking mechanistic analysis of metabolism at single-cell resolution to organ-wide physiology.
- Jack Holcombe
- & Helen Weavers
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Article
| Open AccessAutophagy of OTUD5 destabilizes GPX4 to confer ferroptosis-dependent kidney injury
Understanding the role of GPX4 in cell ferroptosis at the interface of the inner cortex and medulla is crucial in the context of renal injury. Here, the authors demonstrate that the OTUD5 interaction with GPX4 is key in resisting ischemia/reperfusion-induced ferroptosis in renal cells, offering a new strategy for treating acute kidney injury.
- Li-Kai Chu
- , Xu Cao
- & Jun Liu
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Article
| Open AccessCdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice
The role of Cdo1 in exercise-mediated metabolic health and NAFLD is not clear. Here, the authors show that hepatic Cdo1 tethers Camkk2 to AMPK by interacting with both of them, thereby activating AMPK signaling to blunt hepatosteatosis and to promote exercise-mediated alleviation of NAFLD in mice.
- Min Chen
- , Jie-Ying Zhu
- & Liang Guo
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Article
| Open AccessDissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans
To overcome challenges posted by vast number of GPCR genes and redundancy, the authors disrupted nearly all GPCR-encoding genes in C. elegans, enabling effective examination of GPCR signaling and offering a valuable resource for the research community.
- Longjun Pu
- , Jing Wang
- & Changchun Chen
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Review Article
| Open AccessMolecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology
- Nieves Montenegro-Navarro
- , Claudia García-Báez
- & Melissa García-Caballero
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Article
| Open AccessChemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis
Deregulation of BCL-2 proteins ensures resistance to apoptosis. Here, the authors describe cytosolic BAX dimers, which in cancer cells inhibit BAX activation and they develop a strategy to modulate BAX dimers to potentiate BAX-mediated apoptosis.
- Nadege Gitego
- , Bogos Agianian
- & Evripidis Gavathiotis
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Article
| Open AccessRho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles
Cell movements are achieved by the spatio-temporal coordination of local membrane protrusions and retractions. Here, the authors identify a mechanism by which these protrusion and retraction events are coupled and how this affects the directionality of cell movements.
- Suchet Nanda
- , Abram Calderon
- & Leif Dehmelt
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Article
| Open AccessThe function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways
Berkane et al. investigated the activation process of selective autophagy of the ER. They show that that phosphorylation of FAM134 proteins by CK2 is a prerequisite for the formation of large micro-clusters of high-density at the ER membrane.
- Rayene Berkane
- , Hung Ho-Xuan
- & Alexandra Stolz
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Article
| Open AccessA single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs
Dey et al. use structure-function methods to show that partial mimicry of the coatomer-binding motif in the SARS-CoV-2 spike is crucial for its release post coatomer-dependent delivery, thus ensuring optimal spike fusogenicity and VLP incorporation.
- Debajit Dey
- , Enya Qing
- & S. Saif Hasan
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Article
| Open AccessMYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting
SKP2 is an oncogenic E3-ubiquitin ligase. Here the authors show that SKP2 is epigenetically regulated by the muscle lineage transcription factor MYOD, supports tumorigenesis in the Fusion Negative (FN) subtype of rhabdomyosarcoma (RMS) and impairs differentiation promoting degradation of p57Kip2.
- Silvia Pomella
- , Matteo Cassandri
- & Rossella Rota
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Article
| Open AccessUbiquitination-mediated Golgi-to-endosome sorting determines the toxin-antidote duality of fission yeast wtf meiotic drivers
Meiotic drivers of the wtf family kill progeny lacking the driver by producing a toxin and an antidote. Here, authors reveal that ubiquitination-mediated sorting of the antidote prevents it from becoming toxic and enables it to neutralize the toxin.
- Jin-Xin Zheng
- , Tong-Yang Du
- & Li-Lin Du
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Article
| Open AccessMolecular basis and cellular functions of vinculin-actin directional catch bonding
This study provides insights into the directional catch bonding of the linker protein vinculin by elucidating the molecular basis of mechanical reinforcement as well as unveiling its key role in subcellular organization and cellular processes.
- Venkat R. Chirasani
- , Mohammad Ashhar I. Khan
- & Sharon L. Campbell
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Article
| Open AccessOn the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging
Tryptophan metabolism through the kynurenine pathway changes with age and represents a potential intervention target for age associated disease. Here, the authors show that elevating physiological levels of the kynurenine pathway metabolite 3- hydroxyanthranilic acid can promote healthy aging.
- Hope Dang
- , Raul Castro-Portuguez
- & George L. Sutphin
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Article
| Open AccessCytoglobin regulates NO-dependent cilia motility and organ laterality during development
Developmental defects in left-right cardiac determination in humans are associated with ciliary dysfunction and low airway epithelial nitric oxide production. Here, the authors show that cytoglobin is essential for nitric oxide signaling, cilia function, and left-right patterning during zebrafish development.
- Elizabeth R. Rochon
- , Jianmin Xue
- & Paola Corti
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Article
| Open AccessRemodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases
Here, the authors show how the vDUB from the large tegument protein from the human herpes virus can reprogram translation in host cells by modulating the activity of the ribosome quality machinery and activating the integrated stress response.
- Jiangnan Liu
- , Noemi Nagy
- & Maria G. Masucci
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Article
| Open AccessZNF524 directly interacts with telomeric DNA and supports telomere integrity
ZNF524 is a newly described protein that binds to telomeres, the ends of linear chromosomes. ZNF524 promotes the presence of two members of the shelterin complex, TRF2/RAP1, at telomeres, and prevents genomic instability.
- Hanna Braun
- , Ziyan Xu
- & Dennis Kappei
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Article
| Open AccessCENP-A and CENP-B collaborate to create an open centromeric chromatin state
Centromeres are defined by the histone variant CENP-A. Using single-molecule fluorescence and cryoEM, this study shows that CENP-A and the centromeric protein CENP-B collaborate to create dynamic and open chromatin, aiding centromeric factor binding.
- Harsh Nagpal
- , Ahmad Ali-Ahmad
- & Beat Fierz
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Article
| Open AccessSingle-photon microscopy to study biomolecular condensates
The wide variety of cellular processes involving biomolecular condensation makes their quantification a challenging task. Here, the authors present an integrated platform based on single-photon microscopy to study complex biomolecular processes.
- Eleonora Perego
- , Sabrina Zappone
- & Giuseppe Vicidomini
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Article
| Open AccessGRAF1 integrates PINK1-Parkin signaling and actin dynamics to mediate cardiac mitochondrial homeostasis
Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.
- Qiang Zhu
- , Matthew E. Combs
- & Joan M. Taylor
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Article
| Open AccessInterleukin 31 receptor α promotes smooth muscle cell contraction and airway hyperresponsiveness in asthma
Although IL-31 has been implicated in asthma, the exact contribution of the IL-31 receptor (IL-31RA) signalling to airway hyperresponsiveness remains unexplored. Here, the authors demonstrate that IL31RA promotes muscarinic acetylcholine receptor 3 expression and calcium signalling, as well as smooth muscle cell contraction.
- Santhoshi V. Akkenepally
- , Dan J. K. Yombo
- & Satish K. Madala
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Article
| Open AccessThe long non-coding RNA HOTAIR contributes to joint-specific gene expression in rheumatoid arthritis
Although patients with rheumatoid arthritis (RA) usually exhibit symmetrical joint involvement, some can develop alternative patterns of arthritis, often translating into differences in responsiveness to treatment. In this study, the authors propose that the long-noncoding RNA, HOTAIR, might contribute to these differences.
- Muriel Elhai
- , Raphael Micheroli
- & Caroline Ospelt
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Article
| Open AccessThe NERP-4–SNAT2 axis regulates pancreatic β-cell maintenance and function
Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. Here, the authors show a VGF-derived peptide NERP-4 acts as a positive allosteric modulator on the amino acid transporter SNAT2/SLC38A2, thereby contributing to β-cell maintenance and function.
- Weidong Zhang
- , Ayako Miura
- & Masamitsu Nakazato
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Article
| Open AccessContractile ring mechanosensation and its anillin-dependent tuning during early embryogenesis
Contractile ring formation, positioning, and closure is influenced by tissue mechanics, though how this information is transmitted is unclear. Here they show that Anillin is critical for a mechanosensitive pathway that drives cytokinesis and contractile ring closure.
- Christina Rou Hsu
- , Gaganpreet Sangha
- & Kenji Sugioka
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Article
| Open AccessCharacterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis
Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.
- Judith Dönig
- , Hannah Mende
- & Stefan Müller
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Article
| Open AccessNutrient deprivation alters the rate of COPII subunit recruitment at ER subdomains to tune secretory protein transport
Movement of secretory cargoes from the endoplasmic reticulum relies on the COPII protein complex. Here, authors combine gene editing technology with state-of-the-art fluorescence microscopy to define the native dynamics of COPII recruitment at ER subdomains for the first time.
- William Kasberg
- , Peter Luong
- & Anjon Audhya
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Article
| Open AccessStructures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity
Cryo-EM structures reveal the molecular mechanism of ligands and G protein selectivity for prostaglandin F2α receptor, providing guidance for development of better postpartum hemorrhage drugs.
- Xiuqing Lv
- , Kaixuan Gao
- & Xiangyu Liu
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Article
| Open AccessExcess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid–liquid phase separation implicated in myopathy
The prion protein PrPC is known to play a role in skeletal muscle development and physiology, including in myopathy. Here, the authors report that excess PrPC binds microRNAs that enhance its aggregation, which inhibits autophagy in muscle cells.
- Jing Tao
- , Yanping Zeng
- & Yi Liang
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Article
| Open AccessPhospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase
Mitochondria depend on phospholipids supplied by the endoplasmic reticulum. Here, using biochemical assays and molecular dynamics simulations, authors identify VDAC as a scramblase-type lipid transporter that catalyze lipid entry.
- Helene Jahn
- , Ladislav Bartoš
- & Anant K. Menon
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Article
| Open AccessT cell migration requires ion and water influx to regulate actin polymerization
The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.
- Leonard L. de Boer
- , Lesley Vanes
- & Victor L. J. Tybulewicz
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Article
| Open AccessMyeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB
The mechanism underlying thyroid follicle formation is not well understood. Here, the authors show that a subgroup of NF-κB-activated thyrocytes, through interactions with myeloid cells, exhibit increased migration capacity to generate new follicles.
- Yang Rui-Meng
- , Song Shi-Yang
- & Song Huai-Dong
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Article
| Open AccessAtg18 oligomer organization in assembled tubes and on lipid membrane scaffolds
In this work, the authors determined the cryo-EM structures of autophagy-related protein 18 organized in helical tubes and provide insights into the molecular framework for the positioning of downstream components of the autophagy machinery.
- Daniel Mann
- , Simon A. Fromm
- & Carsten Sachse
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Article
| Open AccessThe AMPK-Sirtuin 1-YAP axis is regulated by fluid flow intensity and controls autophagy flux in kidney epithelial cells
Urinary flow is sensed by renal cells but its intensity is dysregulated in renal diseases. Here, the authors report that physiological flow inhibits YAP to promote autophagy, while pathological flow leads to YAP activation and autophagy inhibition.
- Aurore Claude-Taupin
- , Pierre Isnard
- & Nicolas Dupont
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Article
| Open AccessCXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
- Melody Atkins
- , Maud Wurmser
- & Christine Métin
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Article
| Open AccessIntracellular tension sensor reveals mechanical anisotropy of the actin cytoskeleton
Biosensors so far have mostly reported external traction forces exerted against the extracellular matrix or within adhesion receptors. Here, the authors present a sensor that reports molecular tension within the F-actin cytoskeleton.
- Sorosh Amiri
- , Camelia Muresan
- & Michael Murrell
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