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  • UBR E3 ligases and the PDIA3 protease control degradation of unfolded antibody heavy chain by ERAD.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    Danming Tang,Wendy Sandoval,Cynthia Lam,Benjamin Haley,Peter Liu,Di Xue,Deepankar Roy,Tom Patapoff,Salina Louie,Brad Snedecor,Shahram Misaghi

    Accumulation of unfolded antibody chains in the ER triggers ER stress that may lead to reduced productivity in therapeutic antibody manufacturing processes. We identified UBR4 and UBR5 as ubiquitin E3 ligases involved in HC ER-associated degradation. Knockdown of UBR4 and UBR5 resulted in intracellular accumulation, enhanced secretion, and reduced ubiquitination of HC. In concert with these E3 ligases

  • The cell biology of inflammation: From common traits to remarkable immunological adaptations.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    Helen Weavers,Paul Martin

    Tissue damage triggers a rapid and robust inflammatory response in order to clear and repair a wound. Remarkably, many of the cell biology features that underlie the ability of leukocytes to home in to sites of injury and to fight infection-most of which are topics of intensive current research-were originally observed in various weird and wonderful translucent organisms over a century ago by Elie

  • Rab18 regulates focal adhesion dynamics by interacting with kinectin-1 at the endoplasmic reticulum.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    Noemi Antonella Guadagno,Azzurra Margiotta,Synne Arstad Bjørnestad,Linda Hofstad Haugen,Ingrid Kjos,Xiaochun Xu,Xian Hu,Oddmund Bakke,Felix Margadant,Cinzia Progida

    The members of the Rab family of small GTPases are molecular switches that regulate distinct steps in different membrane traffic pathways. In addition to this canonical function, Rabs can play a role in other processes, such as cell adhesion and motility. Here, we reveal the role of the small GTPase Rab18 as a positive regulator of directional migration in chemotaxis, and the underlying mechanism.

  • ULK complex organization in autophagy by a C-shaped FIP200 N-terminal domain dimer.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    Xiaoshan Shi,Adam L Yokom,Chunxin Wang,Lindsey N Young,Richard J Youle,James H Hurley

    The autophagy-initiating human ULK complex consists of the kinase ULK1/2, FIP200, ATG13, and ATG101. Hydrogen-deuterium exchange mass spectrometry was used to map their mutual interactions. The N-terminal 640 residues (NTD) of FIP200 interact with the C-terminal IDR of ATG13. Mutations in these regions abolish their interaction. Negative stain EM and multiangle light scattering showed that FIP200 is

  • TANGLED1 mediates microtubule interactions that may promote division plane positioning in maize.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-23
    Pablo Martinez,Ram Dixit,Rachappa S Balkunde,Antonia Zhang,Seán E O'Leary,Kenneth A Brakke,Carolyn G Rasmussen

    The microtubule cytoskeleton serves as a dynamic structural framework for mitosis in eukaryotic cells. TANGLED1 (TAN1) is a microtubule-binding protein that localizes to the division site and mitotic microtubules and plays a critical role in division plane orientation in plants. Here, in vitro experiments demonstrate that TAN1 directly binds microtubules, mediating microtubule zippering or end-on microtubule

  • Critical role of mitochondrial ubiquitination and the OPTN-ATG9A axis in mitophagy.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-20
    Koji Yamano,Reika Kikuchi,Waka Kojima,Ryota Hayashida,Fumika Koyano,Junko Kawawaki,Takuji Shoda,Yosuke Demizu,Mikihiko Naito,Keiji Tanaka,Noriyuki Matsuda

    Damaged mitochondria are selectively eliminated in a process called mitophagy. Parkin and PINK1, proteins mutated in Parkinson's disease, amplify ubiquitin signals on damaged mitochondria with the subsequent activation of autophagic machinery. Autophagy adaptors are thought to link ubiquitinated mitochondria and autophagy through ATG8 protein binding. Here, we establish methods for inducing mitophagy

  • Cdc42 GTPase regulates ESCRTs in nuclear envelope sealing and ER remodeling.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-20
    Michelle Seiko Lu,David G Drubin

    Small GTPases of the Rho family are binary molecular switches that regulate a variety of processes including cell migration and oriented cell divisions. Known Cdc42 effectors include proteins involved in cytoskeletal remodeling and kinase-dependent transcription induction, but none are involved in the maintenance of nuclear envelope integrity or ER morphology. Maintenance of nuclear envelope integrity

  • Tissue specific requirement of Drosophila Rcd4 for centriole duplication and ciliogenesis.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-17
    Pallavi Panda,Levente Kovacs,Nikola Dzhindzhev,Agnieszka Fatalska,Veronica Persico,Marco Geymonat,Maria Giovanna Riparbelli,Giuliano Callaini,David M Glover

    Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, is suggested to function in centriole elongation and conversion to centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, and reduced basal bodies in sensory organs. Rcd4 interacts with the C-terminal part of Ana3, which loads onto the procentriole during interphase

  • Wbox2: A clathrin terminal domain-derived peptide inhibitor of clathrin-mediated endocytosis.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-11
    Zhiming Chen,Rosa E Mino,Marcel Mettlen,Peter Michaely,Madhura Bhave,Dana Kim Reed,Sandra L Schmid

    Clathrin-mediated endocytosis (CME) occurs via the formation of clathrin-coated vesicles from clathrin-coated pits (CCPs). Clathrin is recruited to CCPs through interactions between the AP2 complex and its N-terminal domain, which in turn recruits endocytic accessory proteins. Inhibitors of CME that interfere with clathrin function have been described, but their specificity and mechanisms of action

  • Coupling of translation quality control and mRNA targeting to stress granules.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-11
    Stephanie L Moon,Tatsuya Morisaki,Timothy J Stasevich,Roy Parker

    Stress granules are dynamic assemblies of proteins and nontranslating RNAs that form when translation is inhibited in response to diverse stresses. Defects in ubiquitin-proteasome system factors including valosin-containing protein (VCP) and the proteasome impact the kinetics of stress granule induction and dissolution as well as being implicated in neuropathogenesis. However, the impacts of dysregulated

  • LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    João Gonçalves,Amit Sharma,Étienne Coyaud,Estelle M N Laurent,Brian Raught,Laurence Pelletier

    Cilia and flagella are microtubule-based cellular projections with important sensory and motility functions. Their absence or malfunction is associated with a growing number of human diseases collectively referred to as ciliopathies. However, the fundamental mechanisms underpinning cilia biogenesis and functions remain only partly understood. Here, we show that depleting LUZP1 or its interacting protein

  • Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-07-06
    Hélène Henrie,Dalal Bakhos-Douaihy,Isabelle Cantaloube,Antoine Pilon,Maya Talantikite,Virginie Stoppin-Mellet,Anita Baillet,Christian Poüs,Béatrice Benoit

    The stress-induced c-Jun N-terminal kinase (JNK) controls microtubule dynamics by enhancing both microtubule growth and rescues. Here, we show that upon cell stress, JNK directly phosphorylates the microtubule rescue factor CLIP-170 in its microtubule-binding domain to increase its rescue-promoting activity. Phosphomimetic versions of CLIP-170 enhance its ability to promote rescue events in vitro and

  • Polar relaxation by dynein-mediated removal of cortical myosin II.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-05
    Bernardo Chapa-Y-Lazo,Motonari Hamanaka,Alexander Wray,Mohan K Balasubramanian,Masanori Mishima

    Nearly six decades ago, Lewis Wolpert proposed the relaxation of the polar cell cortex by the radial arrays of astral microtubules as a mechanism for cleavage furrow induction. While this mechanism has remained controversial, recent work has provided evidence for polar relaxation by astral microtubules, although its molecular mechanisms remain elusive. Here, using C. elegans embryos, we show that polar

  • The +TIP Navigator-1 is an actin-microtubule crosslinker that regulates axonal growth cone motility.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-05
    Carlos Sánchez-Huertas,Marion Bonhomme,Amandine Falco,Christine Fagotto-Kaufmann,Jeffrey van Haren,Freddy Jeanneteau,Niels Galjart,Anne Debant,Jérôme Boudeau

    Microtubule (MT) plus-end tracking proteins (+TIPs) are central players in the coordination between the MT and actin cytoskeletons in growth cones (GCs) during axon guidance. The +TIP Navigator-1 (NAV1) is expressed in the developing nervous system, yet its neuronal functions remain poorly elucidated. Here, we report that NAV1 controls the dynamics and motility of the axonal GCs of cortical neurons

  • ERdj8 governs the size of autophagosomes during the formation process.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-04
    Yo-Hei Yamamoto,Ayano Kasai,Hiroko Omori,Tomoe Takino,Munechika Sugihara,Tetsuo Umemoto,Maho Hamasaki,Tomohisa Hatta,Tohru Natsume,Richard I Morimoto,Ritsuko Arai,Satoshi Waguri,Miyuki Sato,Ken Sato,Shoshana Bar-Nun,Tamotsu Yoshimori,Takeshi Noda,Kazuhiro Nagata

    In macroautophagy, membrane structures called autophagosomes engulf substrates and deliver them for lysosomal degradation. Autophagosomes enwrap a variety of targets with diverse sizes, from portions of cytosol to larger organelles. However, the mechanism by which autophagosome size is controlled remains elusive. We characterized a novel ER membrane protein, ERdj8, in mammalian cells. ERdj8 localizes

  • Protrudin-mediated ER-endosome contact sites promote MT1-MMP exocytosis and cell invasion.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-02
    Nina Marie Pedersen,Eva Maria Wenzel,Ling Wang,Sandra Antoine,Philippe Chavrier,Harald Stenmark,Camilla Raiborg

    Cancer cells break tissue barriers by use of small actin-rich membrane protrusions called invadopodia. Complete invadopodia maturation depends on protrusion outgrowth and the targeted delivery of the matrix metalloproteinase MT1-MMP via endosomal transport by mechanisms that are not known. Here, we show that the ER protein Protrudin orchestrates invadopodia maturation and function. Protrudin formed

  • Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-02
    Natalia Pacheco-Fernandez,Mehrshad Pakdel,Birgit Blank,Ismael Sanchez-Gonzalez,Kathrin Weber,Mai Ly Tran,Tobias Karl-Heinz Hecht,Renate Gautsch,Gisela Beck,Franck Perez,Angelika Hausser,Stefan Linder,Julia von Blume

    Matrix metalloproteinases (MMPs) degrade several ECM components and are crucial modulators of cell invasion and tissue organization. Although much has been reported about their function in remodeling ECM in health and disease, their trafficking across the Golgi apparatus remains poorly understood. Here we report that the cis-Golgi protein nucleobindin-1 (NUCB1) is critical for MMP2 and MT1-MMP trafficking

  • In situ cryo-electron tomography reveals filamentous actin within the microtubule lumen.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-02
    Danielle M Paul,Judith Mantell,Ufuk Borucu,Jennifer Coombs,Katherine J Surridge,John M Squire,Paul Verkade,Mark P Dodding

    Microtubules and filamentous (F-) actin engage in complex interactions to drive many cellular processes from subcellular organization to cell division and migration. This is thought to be largely controlled by proteins that interface between the two structurally distinct cytoskeletal components. Here, we use cryo-electron tomography to demonstrate that the microtubule lumen can be occupied by extended

  • Independent anterograde transport and retrograde cotransport of domain components of myelinated axons.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Yoko Bekku,James L Salzer

    Neurons are highly polarized cells organized into functionally and molecularly distinct domains. A key question is whether the multiprotein complexes that comprise these domains are preassembled, transported, and inserted as a complex or whether their components are transported independently and assemble locally. Here, we have dynamically imaged, in pairwise combinations, the vesicular transport of

  • Prolonged mitosis results in structurally aberrant and over-elongated centrioles.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Dong Kong,Natalie Sahabandu,Catherine Sullenberger,Alejandra Vásquez-Limeta,Delgermaa Luvsanjav,Kimberly Lukasik,Jadranka Loncarek

    Centrioles are precisely built microtubule-based structures that assemble centrosomes and cilia. Aberrations in centriole structure are common in tumors, yet how these aberrations arise is unknown. Analysis of centriole structure is difficult because it requires demanding electron microscopy. Here we employ expansion microscopy to study the origins of centriole structural aberrations in large populations

  • Mitochondrial translation and dynamics synergistically extend lifespan in C. elegans through HLH-30.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Yasmine J Liu,Rebecca L McIntyre,Georges E Janssens,Evan G Williams,Jiayi Lan,Michel van Weeghel,Bauke Schomakers,Henk van der Veen,Nicole N van der Wel,Pallas Yao,William B Mair,Ruedi Aebersold,Alyson W MacInnes,Riekelt H Houtkooper

    Mitochondrial form and function are closely interlinked in homeostasis and aging. Inhibiting mitochondrial translation is known to increase lifespan in C. elegans, and is accompanied by a fragmented mitochondrial network. However, whether this link between mitochondrial translation and morphology is causal in longevity remains uncharacterized. Here, we show in C. elegans that disrupting mitochondrial

  • Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    G Lorenzo Odierna,Sarah K Kerwin,Lucy E Harris,Grace Ji-Eun Shin,Nickolas A Lavidis,Peter G Noakes,S Sean Millard

    Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous

  • Factors promoting nuclear envelope assembly independent of the canonical ESCRT pathway.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    I-Ju Lee,Ema Stokasimov,Nathaniel Dempsey,Joseph M Varberg,Etai Jacob,Sue L Jaspersen,David Pellman

    The nuclear envelope (NE) undergoes dynamic remodeling to maintain NE integrity, a process involving the inner nuclear membrane protein LEM2 recruiting CHMP7/Cmp7 and then ESCRT-III. However, prior work has hinted at CHMP7/ESCRT-independent mechanisms. To identify such mechanisms, we studied NE assembly in Schizosaccharomyces japonicus, a fission yeast that undergoes partial mitotic NE breakdown and

  • Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Mark Jackman,Chiara Marcozzi,Martina Barbiero,Mercedes Pardo,Lu Yu,Adam L Tyson,Jyoti S Choudhary,Jonathon Pines

    How the cell rapidly and completely reorganizes its architecture when it divides is a problem that has fascinated researchers for almost 150 yr. We now know that the core regulatory machinery is highly conserved in eukaryotes, but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major

  • TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-27
    Yui Tomioka,Tetsuya Kotani,Hiromi Kirisako,Yu Oikawa,Yayoi Kimura,Hisashi Hirano,Yoshinori Ohsumi,Hitoshi Nakatogawa

    The mechanisms underlying turnover of the nuclear pore complex (NPC) and the component nucleoporins (Nups) are still poorly understood. In this study, we found that the budding yeast Saccharomyces cerevisiae triggers NPC degradation by autophagy upon the inactivation of Tor kinase complex 1. This degradation largely depends on the selective autophagy-specific factor Atg11 and the autophagy receptor-binding

  • PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Xiaozheng Xu,Bowen Hou,Amitkumar Fulzele,Takeya Masubuchi,Yunlong Zhao,Zijun Wu,Yanyan Hu,Yong Jiang,Yanzhe Ma,Haopeng Wang,Eric J Bennett,Guo Fu,Enfu Hui

    Blockade antibodies of the immunoinhibitory receptor PD-1 can stimulate the anti-tumor activity of T cells, but clinical benefit is limited to a fraction of patients. Evidence suggests that BTLA, a receptor structurally related to PD-1, may contribute to resistance to PD-1 targeted therapy, but how BTLA and PD-1 differ in their mechanisms is debated. Here, we compared the abilities of BTLA and PD-1

  • Reply to "TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium".
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Bing Liu,Muhammad Younus,Suhua Sun,Yiman Li,Yuan Wang,Xi Wu,Xiaoxuan Sun,Shujiang Shang,Changhe Wang,Michael X Zhu,Zhuan Zhou

    In this issue, Gebhardt et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201702151) express interest in our recently published work (Shang et al. 2016. J. Cell Biol.https://doi.org/10.1083/jcb.201603081). Here, we would like to address their concerns regarding the lysosomal TRPA1-mediated intracellular calcium transients in dorsal root ganglion neurons.

  • TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Lisa A Gebhardt,Tetyana I Kichko,Michael J M Fischer,Peter W Reeh

    Shang et al. (2016. J. Cell Biol.https://doi.org/10.1083/jcb.201603081) reported that activation of lysosomal TRPA1 channels led to intracellular calcium transients and CGRP release from DRG neurons. We argue that both findings are more likely due to influx of insufficiently buffered extracellular calcium rather than lysosomal release.

  • Mitochondrial translation, dynamics, and lysosomes combine to extend lifespan.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Levi Ali,Cole M Haynes

    In this issue, Liu et al. (2019. J. Cell. Biol.https://doi.org/10.1083/jcb.201907067) find that the inhibition of mitochondrial ribosomes in combination with impaired mitochondrial fission or fusion increases C. elegans lifespan by activating the transcription factor HLH-30, which promotes lysosomal biogenesis.

  • Fam20C regulates protein secretion by Cab45 phosphorylation.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Tobias Karl-Heinz Hecht,Birgit Blank,Martin Steger,Victor Lopez,Gisela Beck,Bulat Ramazanov,Matthias Mann,Vincent Tagliabracci,Julia von Blume

    The TGN is a key compartment for the sorting and secretion of newly synthesized proteins. At the TGN, soluble proteins are sorted based on the instructions carried in their oligosaccharide backbones or by a Ca2+-mediated process that involves the cargo-sorting protein Cab45. Here, we show that Cab45 is phosphorylated by the Golgi-specific protein kinase Fam20C. Mimicking of phosphorylation translocates

  • Correction: Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Tsutomu Fujito,Wataru Ikeda,Shigeki Kakunaga,Yukiko Minami,Mihoko Kajita,Yasuhisa Sakamoto,Morito Monden,Yoshimi Takai

  • Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Nicolas Joly,Eva Beaumale,Lucie Van Hove,Lisa Martino,Lionel Pintard

    The evolutionarily conserved microtubule (MT)-severing AAA-ATPase enzyme Katanin is emerging as a critical regulator of MT dynamics. In Caenorhabditis elegans, Katanin MT-severing activity is essential for meiotic spindle assembly but is toxic for the mitotic spindle. Here we analyzed Katanin dynamics in C. elegans and deciphered the role of Katanin phosphorylation in the regulation of its activity

  • CRISPR-Cas12a-assisted PCR tagging of mammalian genes.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Julia Fueller,Konrad Herbst,Matthias Meurer,Krisztina Gubicza,Bahtiyar Kurtulmus,Julia D Knopf,Daniel Kirrmaier,Benjamin C Buchmuller,Gislene Pereira,Marius K Lemberg,Michael Knop

    Here we describe a time-efficient strategy for endogenous C-terminal gene tagging in mammalian tissue culture cells. An online platform is used to design two long gene-specific oligonucleotides for PCR with generic template cassettes to create linear dsDNA donors, termed PCR cassettes. PCR cassettes encode the tag (e.g., GFP), a Cas12a CRISPR RNA for cleavage of the target locus, and short homology

  • Protein exchange is reduced in calcium-independent epithelial junctions.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Emily I Bartle,Tejeshwar C Rao,Reena R Beggs,William F Dean,Tara M Urner,Andrew P Kowalczyk,Alexa L Mattheyses

    Desmosomes are cell-cell junctions that provide mechanical integrity to epithelial and cardiac tissues. Desmosomes have two distinct adhesive states, calcium-dependent and hyperadhesive, which balance tissue plasticity and strength. A highly ordered array of cadherins in the adhesive interface is hypothesized to drive hyperadhesion, but how desmosome structure confers adhesive state is still elusive

  • Microtubules keep large cells in shape.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Joyce C M Meiring,Anna Akhmanova

    Migrating cells need to coordinate extension and retraction of their protrusions to avoid fragmenting. Kopf et al. (2020. J. Cell Biol.https://doi.org/10.1083/jcb.201907154) demonstrate that microtubules help to maintain cell coherence during amoeboid migration by controlling actomyosin contractility in retracting protrusions.

  • E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Haohui Duan,Sarah Mansour,Rachel Reed,Margaret K Gillis,Benjamin Parent,Ben Liu,Zsofia Sztupinszki,Nicolai Birkbak,Zoltan Szallasi,Andrew E H Elia,Judy E Garber,Shailja Pathania

    BRCA1/2 help maintain genomic integrity by stabilizing stalled forks. Here, we identify the E3 ligase RFWD3 as an essential modulator of stalled fork stability in BRCA2-deficient cells and show that codepletion of RFWD3 rescues fork degradation, collapse, and cell sensitivity upon replication stress. Stalled forks in BRCA2-deficient cells accumulate phosphorylated and ubiquitinated replication protein

  • Microtubules control cellular shape and coherence in amoeboid migrating cells.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Aglaja Kopf,Jörg Renkawitz,Robert Hauschild,Irute Girkontaite,Kerry Tedford,Jack Merrin,Oliver Thorn-Seshold,Dirk Trauner,Hans Häcker,Klaus-Dieter Fischer,Eva Kiermaier,Michael Sixt

    Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic

  • A PI3K-WIPI2 positive feedback loop allosterically activates LC3 lipidation in autophagy.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-22
    Dorotea Fracchiolla,Chunmei Chang,James H Hurley,Sascha Martens

    Autophagy degrades cytoplasmic cargo by its delivery to lysosomes within double membrane autophagosomes. Synthesis of the phosphoinositide PI(3)P by the autophagic class III phosphatidylinositol-3 kinase complex I (PI3KC3-C1) and conjugation of ATG8/LC3 proteins to phagophore membranes by the ATG12-ATG5-ATG16L1 (E3) complex are two critical steps in autophagosome biogenesis, connected by WIPI2. Here

  • Individual kinetochore-fibers locally dissipate force to maintain robust mammalian spindle structure.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-22
    Alexandra F Long,Pooja Suresh,Sophie Dumont

    At cell division, the mammalian kinetochore binds many spindle microtubules that make up the kinetochore-fiber. To segregate chromosomes, the kinetochore-fiber must be dynamic and generate and respond to force. Yet, how it remodels under force remains poorly understood. Kinetochore-fibers cannot be reconstituted in vitro, and exerting controlled forces in vivo remains challenging. Here, we use microneedles

  • Sas4 links basal bodies to cell division via Hippo signaling.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-22
    Marisa D Ruehle,Alexander J Stemm-Wolf,Chad G Pearson

    Basal bodies (BBs) are macromolecular complexes required for the formation and cortical positioning of cilia. Both BB assembly and DNA replication are tightly coordinated with the cell cycle to ensure their accurate segregation and propagation to daughter cells, but the mechanisms ensuring coordination are unclear. The Tetrahymena Sas4/CPAP protein is enriched at assembling BBs, localizing to the core

  • Ubiquitin links smoothened to intraflagellar transport to regulate Hedgehog signaling.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-22
    Paurav B Desai,Michael W Stuck,Bo Lv,Gregory J Pazour

    In the absence of Hedgehog ligand, patched-1 (Ptch1) localizes to cilia and prevents ciliary accumulation and activation of smoothened (Smo). Upon ligand binding, Ptch1 is removed from cilia, and Smo is derepressed and accumulates in cilia where it activates signaling. The mechanisms regulating these dynamic movements are not well understood, but defects in intraflagellar transport components, including

  • Confounding factors from inducible systems for spatiotemporal gene expression regulation.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-20
    Rob C I Wüst,Riekelt H Houtkooper,Johan Auwerx

    Spatiotemporally regulated targeted gene manipulation is a common way to study the effect of gene variants on phenotypic traits, but the Cre/loxP and Tet-On/Tet-Off systems can affect whole-organism physiology and function due to off-target effects. We highlight some of these adverse effects, including whole-body endocrinology and disturbances in the gut microbiome and in mitochondrial and metabolic

  • Calcineurin-dependent regulation of endocytosis by a plasma membrane ubiquitin ligase adaptor, Rcr1.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-19
    Lu Zhu,Richa Sardana,Daniel K Jin,Scott D Emr

    Rsp5, the Nedd4 family member in yeast, is an E3 ubiquitin ligase involved in numerous cellular processes, many of which require Rsp5 to interact with PY-motif containing adaptor proteins. Here, we show that two paralogous transmembrane Rsp5 adaptors, Rcr1 and Rcr2, are sorted to distinct cellular locations: Rcr1 is a plasma membrane (PM) protein, whereas Rcr2 is sorted to the vacuole. Rcr2 is delivered

  • Fission yeast Pak1 phosphorylates anillin-like Mid1 for spatial control of cytokinesis.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-19
    Joseph O Magliozzi,Jack Sears,Lauren Cressey,Marielle Brady,Hannah E Opalko,Arminja N Kettenbach,James B Moseley

    Protein kinases direct polarized growth by regulating the cytoskeleton in time and space and could play similar roles in cell division. We found that the Cdc42-activated polarity kinase Pak1 colocalizes with the assembling contractile actomyosin ring (CAR) and remains at the division site during septation. Mutations in pak1 led to defects in CAR assembly and genetic interactions with cytokinesis mutants

  • Cargo crowding contributes to sorting stringency in COPII vesicles.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-15
    Natalia Gomez-Navarro,Alejandro Melero,Xiao-Han Li,Jérôme Boulanger,Wanda Kukulski,Elizabeth A Miller

    Accurate maintenance of organelle identity in the secretory pathway relies on retention and retrieval of resident proteins. In the endoplasmic reticulum (ER), secretory proteins are packaged into COPII vesicles that largely exclude ER residents and misfolded proteins by mechanisms that remain unresolved. Here we combined biochemistry and genetics with correlative light and electron microscopy (CLEM)

  • Phosphoregulation provides specificity to biomolecular condensates in the cell cycle and cell polarity.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-14
    Therese M Gerbich,Grace A McLaughlin,Katelyn Cassidy,Scott Gerber,David Adalsteinsson,Amy S Gladfelter

    Biomolecular condensation is a way of organizing cytosol in which proteins and nucleic acids coassemble into compartments. In the multinucleate filamentous fungus Ashbya gossypii, the RNA-binding protein Whi3 regulates the cell cycle and cell polarity through forming macromolecular structures that behave like condensates. Whi3 has distinct spatial localizations and mRNA targets, making it a powerful

  • Structural insights into G domain dimerization and pathogenic mutation of OPA1.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-08
    Caiting Yu,Jinghua Zhao,Liming Yan,Yuanbo Qi,Xiangyang Guo,Zhiyong Lou,Junjie Hu,Zihe Rao

    The fusion of mammalian inner mitochondrial membranes (IMMs) is mediated by dynamin-like GTPase OPA1. Mutations in human OPA1 cause optic atrophy, but the molecular basis for membrane fusion and pathogenesis is not clear. Here, we determined the crystal structure of the minimal GTPase domain (MGD) of human OPA1. A three-helix bundle (HB) domain including two helices extending from the GTPase (G) domain

  • Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-07
    Zhe Chen,Zong-Heng Wang,Guofeng Zhang,Christopher K E Bleck,Dillon J Chung,Grey P Madison,Eric Lindberg,Christian Combs,Robert S Balaban,Hong Xu

    Although mitochondrial DNA (mtDNA) is prone to accumulate mutations and lacks conventional DNA repair mechanisms, deleterious mutations are exceedingly rare. How the transmission of detrimental mtDNA mutations is restricted through the maternal lineage is debated. Here, we demonstrate that mitochondrial fission, together with the lack of mtDNA replication, segregate mtDNA into individual organelles

  • Autophagosome biogenesis: From membrane growth to closure.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Thomas J Melia,Alf H Lystad,Anne Simonsen

    Autophagosome biogenesis involves de novo formation of a membrane that elongates to sequester cytoplasmic cargo and closes to form a double-membrane vesicle (an autophagosome). This process has remained enigmatic since its initial discovery >50 yr ago, but our understanding of the mechanisms involved in autophagosome biogenesis has increased substantially during the last 20 yr. Several key questions

  • KIF14 controls ciliogenesis via regulation of Aurora A and is important for Hedgehog signaling.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Petra Pejskova,Madeline Louise Reilly,Lucia Bino,Ondrej Bernatik,Linda Dolanska,Ranjani Sri Ganji,Zbynek Zdrahal,Alexandre Benmerah,Lukas Cajanek

    Primary cilia play critical roles in development and disease. Their assembly and disassembly are tightly coupled to cell cycle progression. Here, we present data identifying KIF14 as a regulator of cilia formation and Hedgehog (HH) signaling. We show that RNAi depletion of KIF14 specifically leads to defects in ciliogenesis and basal body (BB) biogenesis, as its absence hampers the efficiency of primary

  • Chlamydomonas PKD2 organizes mastigonemes, hair-like glycoprotein polymers on cilia.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Peiwei Liu,Xiaochu Lou,Jenna L Wingfield,Jianfeng Lin,Daniela Nicastro,Karl Lechtreck

    Mutations in the channel protein PKD2 cause autosomal dominant polycystic kidney disease, but the function of PKD2 in cilia remains unclear. Here, we show that PKD2 targets and anchors mastigonemes, filamentous polymers of the glycoprotein MST1, to the extracellular surface of Chlamydomonas cilia. PKD2-mastigoneme complexes physically connect to the axonemal doublets 4 and 8, positioning them perpendicular

  • Torsin ATPase deficiency leads to defects in nuclear pore biogenesis and sequestration of MLF2.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Anthony J Rampello,Ethan Laudermilch,Nidhi Vishnoi,Sarah M Prophet,Lin Shao,Chenguang Zhao,C Patrick Lusk,Christian Schlieker

    Nuclear envelope herniations (blebs) containing FG-nucleoporins and ubiquitin are the phenotypic hallmark of Torsin ATPase manipulation. Both the dynamics of blebbing and the connection to nuclear pore biogenesis remain poorly understood. We employ a proteomics-based approach to identify myeloid leukemia factor 2 (MLF2) as a luminal component of the bleb. Using an MLF2-based live-cell imaging platform

  • SuperPlots: Communicating reproducibility and variability in cell biology.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Samuel J Lord,Katrina B Velle,R Dyche Mullins,Lillian K Fritz-Laylin

    P values and error bars help readers infer whether a reported difference would likely recur, with the sample size n used for statistical tests representing biological replicates, independent measurements of the population from separate experiments. We provide examples and practical tutorials for creating figures that communicate both the cell-level variability and the experimental reproducibility.

  • Ribosome heterogeneity in stem cells and development.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Dan Li,Jianlong Wang

    Translation control is critical to regulate protein expression. By directly adjusting protein levels, cells can quickly respond to dynamic transitions during stem cell differentiation and embryonic development. Ribosomes are multisubunit cellular assemblies that mediate translation. Previously seen as invariant machines with the same composition of components in all conditions, recent studies indicate

  • Sterol biosensor reveals LAM-family Ltc1-dependent sterol flow to endosomes upon Arp2/3 inhibition.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Magdalena Marek,Vincent Vincenzetti,Sophie G Martin

    Sterols are crucial components of biological membranes, which are synthetized in the ER and accumulate in the plasma membrane (PM). Here, by applying a genetically encoded sterol biosensor (D4H), we visualize a sterol flow between PM and endosomes in the fission yeast Schizosaccharomyces pombe. Using time-lapse and correlative light-electron microscopy, we found that inhibition of Arp2/3-dependent

  • MASTL promotes cell contractility and motility through kinase-independent signaling.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-06-01
    Maria Emilia Taskinen,Elisa Närvä,James R W Conway,Laura Soto Hinojosa,Sergio Lilla,Anja Mai,Nicola De Franceschi,Laura L Elo,Robert Grosse,Sara Zanivan,Jim C Norman,Johanna Ivaska

    Microtubule-associated serine/threonine-protein kinase-like (MASTL) is a mitosis-accelerating kinase with emerging roles in cancer progression. However, possible cell cycle-independent mechanisms behind its oncogenicity remain ambiguous. Here, we identify MASTL as an activator of cell contractility and MRTF-A/SRF (myocardin-related transcription factor A/serum response factor) signaling. Depletion

  • Cytoskeletal organization of axons in vertebrates and invertebrates.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-06
    Andreas Prokop

    The maintenance of axons for the lifetime of an organism requires an axonal cytoskeleton that is robust but also flexible to adapt to mechanical challenges and to support plastic changes of axon morphology. Furthermore, cytoskeletal organization has to adapt to axons of dramatically different dimensions, and to their compartment-specific requirements in the axon initial segment, in the axon shaft,

  • RIM-binding protein couples synaptic vesicle recruitment to release sites.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-06
    Astrid G Petzoldt,Torsten W B Götz,Jan Heiner Driller,Janine Lützkendorf,Suneel Reddy-Alla,Tanja Matkovic-Rachid,Sunbin Liu,Elena Knoche,Sara Mertel,Vladimir Ugorets,Martin Lehmann,Niraja Ramesh,Christine Brigitte Beuschel,Benno Kuropka,Christian Freund,Ulrich Stelzl,Bernhard Loll,Fan Liu,Markus C Wahl,Stephan J Sigrist

    At presynaptic active zones, arrays of large conserved scaffold proteins mediate fast and temporally precise release of synaptic vesicles (SVs). SV release sites could be identified by clusters of Munc13, which allow SVs to dock in defined nanoscale relation to Ca2+ channels. We here show in Drosophila that RIM-binding protein (RIM-BP) connects release sites physically and functionally to the ELKS

  • Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-05
    Katy L H Marshall-Phelps,Linde Kegel,Marion Baraban,Torben Ruhwedel,Rafael G Almeida,Maria Rubio-Brotons,Anna Klingseisen,Silvia K Benito-Kwiecinski,Jason J Early,Jenea M Bin,Daumante Suminaite,Matthew R Livesey,Wiebke Möbius,Richard J Poole,David A Lyons

    Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl- (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at

  • Golgi-associated BICD adaptors couple ER membrane penetration and disassembly of a viral cargo.
    J. Cell Biol. (IF 8.811) Pub Date : 2020-05-04
    Chelsey C Spriggs,Somayesadat Badieyan,Kristen J Verhey,Michael A Cianfrocco,Billy Tsai

    During entry, viruses must navigate through the host endomembrane system, penetrate cellular membranes, and undergo capsid disassembly to reach an intracellular destination that supports infection. How these events are coordinated is unclear. Here, we reveal an unexpected function of a cellular motor adaptor that coordinates virus membrane penetration and disassembly. Polyomavirus SV40 traffics to

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