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ULK phosphorylation of STX17 controls autophagosome maturation via FLNA. J. Cell Biol. (IF 7.8) Pub Date : 2023-06-30 Yufen Wang,Huilin Que,ChuangPeng Li,Zhe Wu,Fenglei Jian,Yuan Zhao,Haohao Tang,Yang Chen,Shuaixin Gao,Catherine C L Wong,Ying Li,Chongchong Zhao,Yueguang Rong
Autophagy is a conserved and tightly regulated intracellular quality control pathway. ULK is a key kinase in autophagy initiation, but whether ULK kinase activity also participates in the late stages of autophagy remains unknown. Here, we found that the autophagosomal SNARE protein, STX17, is phosphorylated by ULK at residue S289, beyond which it localizes specifically to autophagosomes. Inhibition
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Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface. J. Cell Biol. (IF 7.8) Pub Date : 2023-03-10 Sergej Limar,Carolin Körner,Fernando Martínez-Montañés,Viktoriya G Stancheva,Verena N Wolf,Stefan Walter,Elizabeth A Miller,Christer S Ejsing,Vanesa Viviana Galassi,Florian Fröhlich
Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells. However, yeast
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KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway. J. Cell Biol. (IF 7.8) Pub Date : 2022-12-08 Yuansong Wan,Momo Morikawa,Manatsu Morikawa,Suguru Iwata,Muhammad Imran Naseer,Adeel Gulzar Ahmed Chaudhary,Yosuke Tanaka,Nobutaka Hirokawa
Epilepsy is a common neurological disease worldwide, and one of its causes is genetic abnormalities. Here, we identified a point mutation in KIF4A, a member of kinesin superfamily molecular motors, in patients with neurological disorders such as epilepsy, developmental delay, and intellectual disability. KIF4 is involved in the poly (ADP-ribose) polymerase (PARP) signaling pathway, and the mutation
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Rac1-PAK1 regulation of Rab11 cycling promotes junction destabilization. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Jennifer C Erasmus,Kasia Smolarczyk,Helena Brezovjakova,Noor F Mohd-Naim,Encarnación Lozano,Karl Matter,Vania M M Braga
Rac1 GTPase is hyperactivated in tumors and contributes to malignancy. Rac1 disruption of junctions requires its effector PAK1, but the precise mechanisms are unknown. Here, we show that E-cadherin is internalized via micropinocytosis in a PAK1-dependent manner without catenin dissociation and degradation. In addition to internalization, PAK1 regulates E-cadherin transport by fine-tuning Rab small
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Caspase inhibition prolongs inflammation by promoting a signaling complex with activated RIPK1. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Xinyue Huang,Shuixia Tan,Yanxia Li,Shuangyi Cao,Xingyan Li,Heling Pan,Bing Shan,Lihui Qian,Junying Yuan
Activation of inflammation by lipopolysaccharide (LPS) is an important innate immune response. Here we investigated the contribution of caspases to the LPS-mediated inflammatory response and discovered distinctive temporal roles of RIPK1 in mediating proinflammatory cytokine production when caspases are inhibited. We propose a biphasic model that differentiates the role of RIPK1 in early versus late
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COPII collar defines the boundary between ER and ER exit site and does not coat cargo containers. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Olga Shomron,Inbar Nevo-Yassaf,Tamar Aviad,Yakey Yaffe,Eitan Erez Zahavi,Anna Dukhovny,Eran Perlson,Ilya Brodsky,Adva Yeheskel,Metsada Pasmanik-Chor,Anna Mironov,Galina V Beznoussenko,Alexander A Mironov,Ella H Sklan,George H Patterson,Yoji Yonemura,Mara Sannai,Christoph Kaether,Koret Hirschberg
COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within the secretory pathway. Live-cell and electron microscopy revealed a novel mode of function for COPII during cargo export from the ER. COPII is recruited to membranes defining the boundary between the ER and ER exit sites, facilitating selective cargo concentration. Using direct observation of living
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Telomere erosion in human pluripotent stem cells leads to ATR-mediated mitotic catastrophe. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Alexandre T Vessoni,Tianpeng Zhang,Annabel Quinet,Ho-Chang Jeong,Michael Munroe,Matthew Wood,Enzo Tedone,Alessandro Vindigni,Jerry W Shay,Roger A Greenberg,Luis F Z Batista
It is well established that short telomeres activate an ATM-driven DNA damage response that leads to senescence in terminally differentiated cells. However, technical limitations have hampered our understanding of how telomere shortening is signaled in human stem cells. Here, we show that telomere attrition induces ssDNA accumulation (G-strand) at telomeres in human pluripotent stem cells (hPSCs),
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Aurora B switches relative strength of kinetochore-microtubule attachment modes for error correction. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Harinath Doodhi,Taciana Kasciukovic,Lesley Clayton,Tomoyuki U Tanaka
To establish chromosome biorientation, aberrant kinetochore-microtubule interaction must be resolved (error correction) by Aurora B kinase. Aurora B differentially regulates kinetochore attachment to the microtubule plus end and its lateral side (end-on and lateral attachment, respectively). However, it is still unclear how kinetochore-microtubule interactions are exchanged during error correction
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EPH/EPHRIN regulates cellular organization by actomyosin contractility effects on cell contacts. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Abigail A Kindberg,Vasudha Srivastava,Jonathon M Muncie,Valerie M Weaver,Zev J Gartner,Jeffrey O Bush
EPH/EPHRIN signaling is essential to many aspects of tissue self-organization and morphogenesis, but little is known about how EPH/EPHRIN signaling regulates cell mechanics during these processes. Here, we use a series of approaches to examine how EPH/EPHRIN signaling drives cellular self-organization. Contact angle measurements reveal that EPH/EPHRIN signaling decreases the stability of heterotypic
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Synaptic activity controls autophagic vacuole motility and function in dendrites. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Vineet Vinay Kulkarni,Anip Anand,Jessica Brandt Herr,Christina Miranda,Maria Chalokh Vogel,Sandra Maday
Macroautophagy (hereafter "autophagy") is a lysosomal degradation pathway that is important for learning and memory, suggesting critical roles for autophagy at the neuronal synapse. Little is known, however, about the molecular details of how autophagy is regulated with synaptic activity. Here, we used live-cell confocal microscopy to define the autophagy pathway in primary hippocampal neurons under
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Lymphocyte egress signal sphingosine-1-phosphate promotes ERM-guided, bleb-based migration. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Tanner F Robertson,Pragati Chengappa,Daniela Gomez Atria,Christine F Wu,Lyndsay Avery,Nathan H Roy,Ivan Maillard,Ryan J Petrie,Janis K Burkhardt
Ezrin, radixin, and moesin (ERM) family proteins regulate cytoskeletal responses by tethering the plasma membrane to the underlying actin cortex. Mutations in ERM proteins lead to severe combined immunodeficiency, but the function of these proteins in T cells remains poorly defined. Using mice in which T cells lack all ERM proteins, we demonstrate a selective role for these proteins in facilitating
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Effector-mediated ERM activation locally inhibits RhoA activity to shape the apical cell domain. J. Cell Biol. (IF 7.8) Pub Date : 2021-06-07 Riasat Zaman,Andrew Lombardo,Cécile Sauvanet,Raghuvir Viswanatha,Valerie Awad,Locke Ezra-Ros Bonomo,David McDermitt,Anthony Bretscher
Activated ezrin-radixin-moesin (ERM) proteins link the plasma membrane to the actin cytoskeleton to generate apical structures, including microvilli. Among many kinases implicated in ERM activation are the homologues LOK and SLK. CRISPR/Cas9 was used to knock out all ERM proteins or LOK/SLK in human cells. LOK/SLK knockout eliminates all ERM-activating phosphorylation. The apical domains of cells lacking
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MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-06 Rafael Deliz-Aguirre,Fakun Cao,Fenja H U Gerpott,Nichanok Auevechanichkul,Mariam Chupanova,YeVin Mun,Elke Ziska,Marcus J Taylor
A recurring feature of innate immune receptor signaling is the self-assembly of signaling proteins into oligomeric complexes. The Myddosome is an oligomeric complex that is required to transmit inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for how Myddosome proteins self-assemble and regulate intracellular signaling remains poorly understood
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Teasing out function from morphology: Similarities between primary cilia and immune synapses. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-06 Tiphaine Douanne,Jane C Stinchcombe,Gillian M Griffiths
Immune synapses are formed between immune cells to facilitate communication and coordinate the immune response. The reorganization of receptors involved in recognition and signaling creates a transient area of plasma membrane specialized in signaling and polarized secretion. Studies on the formation of the immune synapse between cytotoxic T lymphocytes (CTLs) and their targets uncovered a critical
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Lysosome biogenesis: Regulation and functions. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-05 Chonglin Yang,Xiaochen Wang
Lysosomes are degradation centers and signaling hubs in cells and play important roles in cellular homeostasis, development, and aging. Changes in lysosome function are essential to support cellular adaptation to multiple signals and stimuli. Therefore, lysosome biogenesis and activity are regulated by a wide variety of intra- and extracellular cues. Here, we summarize current knowledge of the regulatory
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Elimination of nurse cell nuclei that shuttle into oocytes during oogenesis. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-05 Zehra Ali-Murthy,Richard D Fetter,Wanpeng Wang,Bin Yang,Loic A Royer,Thomas B Kornberg
Drosophila oocytes develop together with 15 sister germline nurse cells (NCs), which pass products to the oocyte through intercellular bridges. The NCs are completely eliminated during stages 12-14, but we discovered that at stage 10B, two specific NCs fuse with the oocyte and extrude their nuclei through a channel that opens in the anterior face of the oocyte. These nuclei extinguish in the ooplasm
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Dbnl and β-catenin promote pro-N-cadherin processing to maintain apico-basal polarity. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Antonio Herrera,Anghara Menendez,Blanca Torroba,Andrea Ochoa,Sebastián Pons
The neural tube forms when neural stem cells arrange into a pseudostratified, single-cell-layered epithelium, with a marked apico-basal polarity, and in which adherens junctions (AJs) concentrate in the subapical domain. We previously reported that sustained β-catenin expression promotes the formation of enlarged apical complexes (ACs), enhancing apico-basal polarity, although the mechanism through
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Hongyuan Yang: Tracking lipids, one droplet at a time. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Melina Casadio
Hongyuan Yang investigates lipid trafficking and lipid droplet biogenesis.
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A TRCky TA protein delivery service snubs the UPS. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Alexander J McQuown,Dvir Reif,Vladimir Denic
In mammals, tail-anchored (TA) proteins that are posttranslationally captured by the chaperone SGTA are triaged by the BAG6 complex into one of two fates: handoff to an ER targeting factor for membrane insertion or polyubiquitination for destruction by the proteasome. In this issue, Culver and Mariappan (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202004086) show that a fraction of newly synthesized
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FIT2 organizes lipid droplet biogenesis with ER tubule-forming proteins and septins. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Fang Chen,Bing Yan,Jie Ren,Rui Lyu,Yanfang Wu,Yuting Guo,Dong Li,Hong Zhang,Junjie Hu
Lipid droplets (LDs) are critical for lipid storage and energy metabolism. LDs form in the endoplasmic reticulum (ER). However, the molecular basis for LD biogenesis remains elusive. Here, we show that fat storage-inducing transmembrane protein 2 (FIT2) interacts with ER tubule-forming proteins Rtn4 and REEP5. The association is mainly transmembrane domain based and stimulated by oleic acid. Depletion
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Time-resolved proteomics profiling of the ciliary Hedgehog response. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Elena A May,Marian Kalocsay,Inès Galtier D'Auriac,Patrick S Schuster,Steven P Gygi,Maxence V Nachury,David U Mick
The primary cilium is a signaling compartment that interprets Hedgehog signals through changes of its protein, lipid, and second messenger compositions. Here, we combine proximity labeling of cilia with quantitative mass spectrometry to unbiasedly profile the time-dependent alterations of the ciliary proteome in response to Hedgehog. This approach correctly identifies the three factors known to undergo
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GRASPing for consensus about the Golgi apparatus. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Christopher G Burd
Cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon. Two proteins, GRASP65 and GRASP55, previously implicated in stacking of cisternae, are shown to be required for the formation of the Golgi ribbon.
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Endoplasmic reticulum maintains ion homeostasis required for plasma membrane repair. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Goutam Chandra,Sen Chandra Sreetama,Davi A G Mázala,Karine Charton,Jack H VanderMeulen,Isabelle Richard,Jyoti K Jaiswal
Of the many crucial functions of the ER, homeostasis of physiological calcium increase is critical for signaling. Plasma membrane (PM) injury causes a pathological calcium influx. Here, we show that the ER helps clear this surge in cytoplasmic calcium through an ER-resident calcium pump, SERCA, and a calcium-activated ion channel, Anoctamin 5 (ANO5). SERCA imports calcium into the ER, and ANO5 supports
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Coupling of Cdc20 inhibition and activation by BubR1. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Jamin B Hein,Dimitriya H Garvanska,Isha Nasa,Arminja N Kettenbach,Jakob Nilsson
Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. This creates a conundrum for how Cdc20 is activated before cyclin B1 degradation
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ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Dakota L Jones,Jeffrey A Meridew,Patrick A Link,Merrick T Ducharme,Katherine L Lydon,Kyoung M Choi,Nunzia Caporarello,Qi Tan,Ana Maria Diaz Espinosa,Yuning Xiong,Jeong-Heon Lee,Zhenqing Ye,Huihuang Yan,Tamas Ordog,Giovanni Ligresti,Xaralabos Varelas,Daniel J Tschumperlin
Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix stiffness to changes in fibroblast phenotype are incompletely understood. Here, we evaluated the effect of matrix stiffness on genome-wide chromatin accessibility in freshly isolated lung fibroblasts using ATAC-seq. We found higher matrix stiffness profoundly increased global chromatin
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Deubiquitinases USP20/33 promote the biogenesis of tail-anchored membrane proteins. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Jacob A Culver,Malaiyalam Mariappan
Numerous proteins that have hydrophobic transmembrane domains (TMDs) traverse the cytosol and posttranslationally insert into cellular membranes. It is unclear how these hydrophobic membrane proteins evade recognition by the cytosolic protein quality control (PQC), which typically recognizes exposed hydrophobicity in misfolded proteins and marks them for proteasomal degradation by adding ubiquitin
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Plk4 triggers autonomous de novo centriole biogenesis and maturation. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Catarina Nabais,Delphine Pessoa,Jorge de-Carvalho,Thomas van Zanten,Paulo Duarte,Satyajit Mayor,Jorge Carneiro,Ivo A Telley,Mónica Bettencourt-Dias
Centrioles form centrosomes and cilia. In most proliferating cells, centrioles assemble through canonical duplication, which is spatially, temporally, and numerically regulated by the cell cycle and the presence of mature centrioles. However, in certain cell types, centrioles assemble de novo, yet by poorly understood mechanisms. Herein, we established a controlled system to investigate de novo centriole
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Cytonemes with complex geometries and composition extend into invaginations of target cells. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Brent M Wood,Valentina Baena,Hai Huang,Danielle M Jorgens,Mark Terasaki,Thomas B Kornberg
Cytonemes are specialized filopodia that mediate paracrine signaling in Drosophila and other animals. Studies using fluorescence confocal microscopy (CM) established their general paths, cell targets, and essential roles in signaling. To investigate details unresolvable by CM, we used high-pressure freezing and EM to visualize cytoneme structures, paths, contents, and contacts. We observed cytonemes
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Reduced insulin/IGF1 signaling prevents immune aging via ZIP-10/bZIP-mediated feedforward loop. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Yujin Lee,Yoonji Jung,Dae-Eun Jeong,Wooseon Hwang,Seokjin Ham,Hae-Eun H Park,Sujeong Kwon,Jasmine M Ashraf,Coleen T Murphy,Seung-Jae V Lee
A hallmark of aging is immunosenescence, a decline in immune functions, which appeared to be inevitable in living organisms, including Caenorhabditis elegans. Here, we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically enhances immunocompetence in old age in C. elegans. We demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase
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mTORC1 activity is supported by spatial association with focal adhesions. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Yoana Rabanal-Ruiz,Adam Byron,Alexander Wirth,Ralitsa Madsen,Lucia Sedlackova,Graeme Hewitt,Glyn Nelson,Julian Stingele,Jimi C Wills,Tong Zhang,André Zeug,Reinhard Fässler,Bart Vanhaesebroeck,Oliver D K Maddocks,Evgeni Ponimaskin,Bernadette Carroll,Viktor I Korolchuk
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogenic and stress signals to control growth and metabolism. Activation of mTORC1 by amino acids and growth factors involves recruitment of the complex to the lysosomal membrane and is further supported by lysosome distribution to the cell periphery. Here, we show that translocation of lysosomes toward the cell periphery brings mTORC1
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Microtubules form by progressively faster tubulin accretion, not by nucleation-elongation. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Luke M Rice,Michelle Moritz,David A Agard
Microtubules are dynamic polymers that play fundamental roles in all eukaryotes. Despite their importance, how new microtubules form is poorly understood. Textbooks have focused on variations of a nucleation-elongation mechanism in which monomers rapidly equilibrate with an unstable oligomer (nucleus) that limits the rate of polymer formation; once formed, the polymer then elongates efficiently from
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Parameter-free molecular super-structures quantification in single-molecule localization microscopy. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Mattia Marenda,Elena Lazarova,Sebastian van de Linde,Nick Gilbert,Davide Michieletto
Understanding biological function requires the identification and characterization of complex patterns of molecules. Single-molecule localization microscopy (SMLM) can quantitatively measure molecular components and interactions at resolutions far beyond the diffraction limit, but this information is only useful if these patterns can be quantified and interpreted. We provide a new approach for the
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FUS-dependent liquid-liquid phase separation is important for DNA repair initiation. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Brunno R Levone,Silvia C Lenzken,Marco Antonaci,Andreas Maiser,Alexander Rapp,Francesca Conte,Stefan Reber,Jonas Mechtersheimer,Antonella E Ronchi,Oliver Mühlemann,Heinrich Leonhardt,M Cristina Cardoso,Marc-David Ruepp,Silvia M L Barabino
RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid-liquid phase separation (LLPS) in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS
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ALS2 regulates endosomal trafficking, postsynaptic development, and neuronal survival. J. Cell Biol. (IF 7.8) Pub Date : 2021-05-03 Joohyung Kim,Sungdae Kim,Minyeop Nahm,Tsai-Ning Li,Hsin-Chieh Lin,Yeongjin David Kim,Jihye Lee,Chi-Kuang Yao,Seungbok Lee
Mutations in the human ALS2 gene cause recessive juvenile-onset amyotrophic lateral sclerosis and related motor neuron diseases. Although the ALS2 protein has been identified as a guanine-nucleotide exchange factor for the small GTPase Rab5, its physiological roles remain largely unknown. Here, we demonstrate that the Drosophila homologue of ALS2 (dALS2) promotes postsynaptic development by activating
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O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-29 Tae Yeon Yoo,Timothy J Mitchison
Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine
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Mechanism of mutant calreticulin-mediated activation of the thrombopoietin receptor in cancers. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-29 Arunkumar Venkatesan,Jie Geng,Malathi Kandarpa,Sanjeeva Joseph Wijeyesakere,Ashwini Bhide,Moshe Talpaz,Irina D Pogozheva,Malini Raghavan
Myeloproliferative neoplasms (MPNs) are frequently driven by mutations within the C-terminal domain (C-domain) of calreticulin (CRT). CRTDel52 and CRTIns5 are recurrent mutations. Oncogenic transformation requires both mutated CRT and the thrombopoietin receptor (Mpl), but the molecular mechanism of CRT-mediated constitutive activation of Mpl is unknown. We show that the acquired C-domain of CRTDel52
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Centromeric transcription maintains centromeric cohesion in human cells. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-22 Yujue Chen,Qian Zhang,Zhen Teng,Hong Liu
Centromeric transcription has been shown to play an important role in centromere functions. However, lack of approaches to specifically manipulate centromeric transcription calls into question that the proposed functions are a direct consequence of centromeric transcription. By monitoring nascent RNAs, we found that several transcriptional inhibitors exhibited distinct, even opposing, efficacies on
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Lose it to use it. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Seth G Haddix,Matthew N Rasband
In this issue, Wang et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.201911114) describe a phenomenon in which neuromuscular junction synapse elimination triggers myelination of terminal motor axon branches. They propose a mechanism initiated by synaptic pruning that depends on synaptic activity, cytoskeletal maturation, and the associated anterograde transport of trophic factors including Neuregulin
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Straightening up is required to nucleate new microtubules. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Melissa K Gardner
In this issue, Ayukawa, Iwata, Imai, and colleagues (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202007033) use rapid temporal and high-spatial-resolution electron microscopy imaging to examine the earliest stages of new microtubule nucleation. They discover that straightening of curved tubulin oligomers increases the efficiency of microtubule nucleation.
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Design of genetically encoded sensors to detect nucleosome ubiquitination in live cells. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Carolina Dos Santos Passos,Yun-Seok Choi,Christopher D Snow,Tingting Yao,Robert E Cohen
Histone posttranslational modifications (PTMs) are dynamic, context-dependent signals that modulate chromatin structure and function. Ubiquitin (Ub) conjugation to different lysines of histones H2A and H2B is used to regulate diverse processes such as gene silencing, transcriptional elongation, and DNA repair. Despite considerable progress made to elucidate the players and mechanisms involved in histone
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GTP-dependent formation of straight tubulin oligomers leads to microtubule nucleation. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Rie Ayukawa,Seigo Iwata,Hiroshi Imai,Shinji Kamimura,Masahito Hayashi,Kien Xuan Ngo,Itsushi Minoura,Seiichi Uchimura,Tsukasa Makino,Mikako Shirouzu,Hideki Shigematsu,Ken Sekimoto,Benoît Gigant,Etsuko Muto
Nucleation of microtubules (MTs) is essential for cellular activities, but its mechanism is unknown because of the difficulty involved in capturing rare stochastic events in the early stage of polymerization. Here, combining rapid flush negative stain electron microscopy (EM) and kinetic analysis, we demonstrate that the formation of straight oligomers of critical size is essential for nucleation.
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Completion of neuronal remodeling prompts myelination along developing motor axon branches. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Mengzhe Wang,Tatjana Kleele,Yan Xiao,Gabriela Plucinska,Petros Avramopoulos,Stefan Engelhardt,Markus H Schwab,Matthias Kneussel,Tim Czopka,Diane L Sherman,Peter J Brophy,Thomas Misgeld,Monika S Brill
Neuronal remodeling and myelination are two fundamental processes during neurodevelopment. How they influence each other remains largely unknown, even though their coordinated execution is critical for circuit function and often disrupted in neuropsychiatric disorders. It is unclear whether myelination stabilizes axon branches during remodeling or whether ongoing remodeling delays myelination. By modulating
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Interviewing for a PI position-the pandemic way. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Melina Casadio,Dan Simon
JCB asks early career researchers to share their experience interviewing for academic faculty positions and becoming independent PIs during the COVID-19 pandemic.
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Autophagy facilitates mitochondrial rebuilding after acute heat stress via a DRP-1-dependent process. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Yanfang Chen,Romane Leboutet,Céline Largeau,Siham Zentout,Christophe Lefebvre,Agnès Delahodde,Emmanuel Culetto,Renaud Legouis
Acute heat stress (aHS) can induce strong developmental defects in Caenorhabditis elegans larva but not lethality or sterility. This stress results in transitory fragmentation of mitochondria, formation of aggregates in the matrix, and decrease of mitochondrial respiration. Moreover, active autophagic flux associated with mitophagy events enables the rebuilding of the mitochondrial network and developmental
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A dimmer switch for endosome-to-cell surface recycling. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Matthew N J Seaman
Endosome-to-cell surface recycling is mediated by retromer and Snx27. In this issue, Mao et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.202010048) detail how endosomal protein sorting responds to external stimuli and reveal that phosphorylation of Snx27 regulates its cargo-binding function resulting in reduced endosome-to-cell surface recycling.
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The cell biology of Parkinson's disease. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Nikhil Panicker,Preston Ge,Valina L Dawson,Ted M Dawson
Parkinson's disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopamine neurons in the substantia nigra pars compacta. Our understanding of PD biology has been enriched by the identification of genes involved in its rare, inheritable forms, termed PARK genes. These genes encode proteins including α-syn, LRRK2, VPS35, parkin, PINK1, and DJ1, which can cause monogenetic
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Pluripotency state regulates cytoneme selectivity and self-organization of embryonic stem cells. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Sergi Junyent,Joshua Reeves,Eileen Gentleman,Shukry J Habib
To coordinate cell fate with changes in spatial organization, stem cells (SCs) require specific and adaptable systems of signal exchange and cell-to-cell communication. Pluripotent embryonic stem cells (ESCs) use cytonemes to pair with trophoblast stem cells (TSCs) and form synthetic embryonic structures in a Wnt-dependent manner. How these interactions vary with pluripotency states remains elusive
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Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Lejiao Mao,Chenyi Liao,Jiao Qin,Yanqiu Gong,Yifei Zhou,Shasha Li,Zhe Liu,Huaqing Deng,Wankun Deng,Qingxiang Sun,Xianming Mo,Yu Xue,Daniel D Billadeau,Lunzhi Dai,Guohui Li,Da Jia
Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through
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SUV39H2 epigenetic silencing controls fate conversion of epidermal stem and progenitor cells. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Pierre Balmer,William V J Hariton,Beyza S Sayar,Vidhya Jagannathan,Arnaud Galichet,Tosso Leeb,Petra Roosje,Eliane J Müller
Epigenetic histone trimethylation on lysine 9 (H3K9me3) represents a major molecular signal for genome stability and gene silencing conserved from worms to man. However, the functional role of the H3K9 trimethylases SUV39H1/2 in mammalian tissue homeostasis remains largely unknown. Here, we use a spontaneous dog model with monogenic inheritance of a recessive SUV39H2 loss-of-function variant and impaired
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Phase separation of Axin organizes the β-catenin destruction complex. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Junxiu Nong,Kexin Kang,Qiaoni Shi,Xuechen Zhu,Qinghua Tao,Ye-Guang Chen
In Wnt/β-catenin signaling, the β-catenin protein level is deliberately controlled by the assembly of the multiprotein β-catenin destruction complex composed of Axin, adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), casein kinase 1α (CK1α), and others. Here we provide compelling evidence that formation of the destruction complex is driven by protein liquid-liquid phase separation
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Correction: Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Sebastian Schuck,William A Prinz,Kurt S Thorn,Christiane Voss,Peter Walter
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Superresolution characterization of core centriole architecture. J. Cell Biol. (IF 7.8) Pub Date : 2021-04-05 Yuan Tian,Chenxi Wei,Jianfeng He,Yuxuan Yan,Nan Pang,Xiaomin Fang,Xin Liang,Jingyan Fu
The centrosome is the main microtubule-organizing center in animal cells. It comprises of two centrioles and the surrounding pericentriolar material. Protein organization at the outer layer of the centriole and outward has been studied extensively; however, an overall picture of the protein architecture at the centriole core has been missing. Here we report a direct view of Drosophila centriolar proteins
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Correction: An early endosome-derived retrograde trafficking pathway promotes secretory granule maturation. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Cheng-I J Ma,Yitong Yang,Taeah Kim,Chang Hua Chen,Gordon Polevoy,Miluska VIssa,Jason Burgess,Julie A Brill
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Starting a lab during the COVID-19 pandemic. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Melina Casadio,Dan Simon
JCB asks early career investigators to share their experience launching a lab during the COVID-19 pandemic.
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Mechanisms of nonvesicular lipid transport. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Karin M Reinisch,William A Prinz
We have long known that lipids traffic between cellular membranes via vesicles but have only recently appreciated the role of nonvesicular lipid transport. Nonvesicular transport can be high volume, supporting biogenesis of rapidly expanding membranes, or more targeted and precise, allowing cells to rapidly alter levels of specific lipids in membranes. Most such transport probably occurs at membrane
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Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Matteo Audano,Silvia Pedretti,Simona Ligorio,Francesco Gualdrini,Sara Polletti,Marta Russo,Serena Ghisletti,Camilla Bean,Maurizio Crestani,Donatella Caruso,Emma De Fabiani,Nico Mitro
The commitment of mesenchymal stem cells to preadipocytes is stimulated by hormonal induction. Preadipocytes induced to differentiate repress protein synthesis, remodel their cytoskeleton, and increase mitochondrial function to support anabolic pathways. These changes enable differentiation into mature adipocytes. Our understanding of the factors that coordinately regulate the early events of adipocyte
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Brd4 regulates NLRC4 inflammasome activation by facilitating IRF8-mediated transcription of Naips. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Xingchen Dong,Xiangming Hu,Yan Bao,Guo Li,Xiao-Dong Yang,James M Slauch,Lin-Feng Chen
NLRC4 inflammasome activation and the subsequent maturation of IL-1β and IL-18 are critical for protection against infection by bacterial pathogens. The epigenetic regulator Brd4 has emerged as a key player in inflammation by regulating the expression of inflammatory cytokines. However, whether Brd4 has any role in inflammasome activation remains undetermined. Here, we demonstrated that Brd4 is an
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The N-terminus of Sfi1 and yeast centrin Cdc31 provide the assembly site for a new spindle pole body. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Diana Rüthnick,Jlenia Vitale,Annett Neuner,Elmar Schiebel
The spindle pole body (SPB) provides microtubule-organizing functions in yeast and duplicates exactly once per cell cycle. The first step in SPB duplication is the half-bridge to bridge conversion via the antiparallel dimerization of the centrin (Cdc31)-binding protein Sfi1 in anaphase. The bridge, which is anchored to the old SPB on the proximal end, exposes free Sfi1 N-termini (N-Sfi1) at its distal
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High-fidelity reconstitution of stress granules and nucleoli in mammalian cellular lysate. J. Cell Biol. (IF 7.8) Pub Date : 2021-03-01 Brian D Freibaum,James Messing,Peiguo Yang,Hong Joo Kim,J Paul Taylor
Liquid-liquid phase separation (LLPS) is a mechanism of intracellular organization that underlies the assembly of a variety of RNP granules. Fundamental biophysical principles governing LLPS during granule assembly have been revealed by simple in vitro systems, but these systems have limitations when studying the biology of complex, multicomponent RNP granules. Visualization of RNP granules in cells