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Reticular adhesions are assembled at flat clathrin lattices and opposed by active integrin α5β1. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-26 Laura Hakanpää,Amr Abouelezz,An-Sofie Lenaerts,Seyda Culfa,Michael Algie,Jenny Bärlund,Pekka Katajisto,Harvey McMahon,Leonardo Almeida-Souza
Reticular adhesions (RAs) consist of integrin αvβ5 and harbor flat clathrin lattices (FCLs), long-lasting structures with similar molecular composition as clathrin-mediated endocytosis (CME) carriers. Why FCLs and RAs colocalize is not known. Here, we show that RAs are assembled at FCLs in a process controlled by fibronectin (FN) and its receptor, integrin α5β1. We observed that cells on FN-rich matrices
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Riding up the escaLEC-TOR for valvular health. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-25 Zolt Arany
Endothelial-lined valves assure unidirectional flow in the lymphatic system. In this issue, Saygili Demir et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202207049) demonstrate how continuous repair of these valves occur, beginning with mTOR-activated cell replication in valve sinuses, and followed by cell migration to cover the valve surface.
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Autoinhibitory mechanism controls binding of centrosomin motif 1 to γ-tubulin ring complex. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-22 Shaozhong Yang,Franco K C Au,Gefei Li,Jianwei Lin,Xiang David Li,Robert Z Qi
The γ-tubulin ring complex (γTuRC) is the principal nucleator of cellular microtubules, and the microtubule-nucleating activity of the complex is stimulated by binding to the γTuRC-mediated nucleation activator (γTuNA) motif. The γTuNA is part of the centrosomin motif 1 (CM1), which is widely found in γTuRC stimulators, including CDK5RAP2. Here, we show that a conserved segment within CM1 binds to
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Inhibition of endolysosome fusion increases exosome secretion. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-22 Ganesh Vilas Shelke,Chad D Williamson,Michal Jarnik,Juan S Bonifacino
Exosomes are small vesicles that are secreted from cells to dispose of undegraded materials and mediate intercellular communication. A major source of exosomes is intraluminal vesicles within multivesicular endosomes that undergo exocytic fusion with the plasma membrane. An alternative fate of multivesicular endosomes is fusion with lysosomes, resulting in degradation of the intraluminal vesicles.
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Small lipid droplets are rigid enough to indent a nucleus, dilute the lamina, and cause rupture. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-22 Irena L Ivanovska,Michael P Tobin,Tianyi Bai,Lawrence J Dooling,Dennis E Discher
The nucleus in many cell types is a stiff organelle, but fat-filled lipid droplets (FDs) in cytoplasm are seen to indent and displace the nucleus. FDs are phase-separated liquids with a poorly understood interfacial tension γ that determines how FDs interact with other organelles. Here, micron-sized FDs remain spherical as they indent peri-nuclear actomyosin and the nucleus, while causing local dilution
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Cingulin and paracingulin tether myosins-2 to junctions to mechanoregulate the plasma membrane. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-19 Florian Rouaud,Wenmao Huang,Arielle Flinois,Kunalika Jain,Ekaterina Vasileva,Thomas Di Mattia,Marine Mauperin,David A D Parry,Vera Dugina,Christine Chaponnier,Isabelle Méan,Sylvie Montessuit,Annick Mutero-Maeda,Jie Yan,Sandra Citi
The mechanisms that regulate the spatial sorting of nonmuscle myosins-2 (NM2) isoforms and couple them mechanically to the plasma membrane are unclear. Here we show that the cytoplasmic junctional proteins cingulin (CGN) and paracingulin (CGNL1) interact directly with NM2s through their C-terminal coiled-coil sequences. CGN binds strongly to NM2B, and CGNL1 to NM2A and NM2B. Knockout (KO), exogenous
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Giant worm-shaped ESCRT scaffolds surround actin-independent integrin clusters. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-18 Femmy C Stempels,Muwei Jiang,Harry M Warner,Magda-Lena Moser,Maaike H Janssens,Sjors Maassen,Iris H Nelen,Rinse de Boer,William F Jiemy,David Knight,Julian Selley,Ronan O'Cualain,Maksim V Baranov,Thomas C Q Burgers,Roberto Sansevrino,Dragomir Milovanovic,Peter Heeringa,Matthew C Jones,Rifka Vlijm,Martin Ter Beest,Geert van den Bogaart
Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles. Here, we discovered micrometer-sized worm-shaped ESCRT structures that stably persist for multiple hours at the plasma membrane of macrophages, dendritic cells, and fibroblasts. These structures surround clusters of integrins
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A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-18 Tino Pleiner,Masami Hazu,Giovani Pinton Tomaleri,Vy N Nguyen,Kurt Januszyk,Rebecca M Voorhees
Tail-anchored (TA) proteins play essential roles in mammalian cells, and their accurate localization is critical for proteostasis. Biophysical similarities lead to mistargeting of mitochondrial TA proteins to the ER, where they are delivered to the insertase, the ER membrane protein complex (EMC). Leveraging an improved structural model of the human EMC, we used mutagenesis and site-specific crosslinking
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The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-17 Aya Mizuike,Shota Sakai,Kaoru Katoh,Toshiyuki Yamaji,Kentaro Hanada
Phosphatidylinositol 4-monophosphate [PtdIns(4)P] is a precursor for various phosphoinositides but also a membrane-embedded component crucial for membrane contact sites (MCSs). Several lipid transfer proteins are recruited to MCSs by recognizing PtdIns(4)P; however, it remains poorly elucidated how the production of PtdIns(4)P for lipid transport at MCSs is regulated. Following human genome-wide screening
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Not just protons: Chloride also activates lysosomal acidic hydrolases. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-16 Xinghua Feng,Siyu Liu,Haoxing Xu
Lysosomal hydrolases require an acidic lumen for their optimal activities. In this issue, two independent groups (Wu et al. 2023. J. Cell Biol.https://doi.org/10.1083/jcb.202208155; Zhang et al. 2023. J. Cell. Biol.https://doi.org/10.1083/jcb.202210063) report that hydrolase activation also requires high intralysosomal Cl-, which is established by the lysosomal Cl-/H+ exchanger ClC-7.
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CLASPs stabilize the pre-catastrophe intermediate state between microtubule growth and shrinkage. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-15 Elizabeth J Lawrence,Saptarshi Chatterjee,Marija Zanic
Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth and shrinkage. How CLASPs specifically modulate microtubule transitions is not understood. Here, we investigate the effects of CLASPs on the pre-catastrophe
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Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-11 Sneha Parmar,Samuel J Gonzalez,Julia M Heckel,Soumya Mukherjee,Mark McClellan,Duncan J Clarke,Marnie Johansson,Damien Tank,Athena Geisness,David K Wood,Melissa K Gardner
During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches
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A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-09 Esra Peker,Konstantin Weiss,Jiyao Song,Christine Zarges,Sarah Gerlich,Volker Boehm,Aleksandra Trifunovic,Thomas Langer,Niels H Gehring,Thomas Becker,Jan Riemer
Mitochondria critically rely on protein import and its tight regulation. Here, we found that the complex I assembly factor NDUFAF8 follows a two-step import pathway linking IMS and matrix import systems. A weak targeting sequence drives TIM23-dependent NDUFAF8 matrix import, and en route, allows exposure to the IMS disulfide relay, which oxidizes NDUFAF8. Import is closely surveyed by proteases: YME1L
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Triggered Golgi membrane enrichment promotes PtdIns(4,5)P2 generation for plasma membrane repair. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-09 Xinan Meng,Chandra Sugiarto Wijaya,Qingfang Shao,Suhong Xu
The maintenance of plasma membrane integrity and a capacity for efficiently repairing damaged membranes are essential for cell survival. Large-scale wounding depletes various membrane components at the wound sites, including phosphatidylinositols, yet little is known about how phosphatidylinositols are generated after depletion. Here, working with our in vivo C. elegans epidermal cell wounding model
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Distinct domains in Ndc1 mediate its interaction with the Nup84 complex and the nuclear membrane. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-08 Ingo Amm,Marion Weberruss,Andrea Hellwig,Johannes Schwarz,Marianna Tatarek-Nossol,Christian Lüchtenborg,Martina Kallas,Britta Brügger,Ed Hurt,Wolfram Antonin
Nuclear pore complexes (NPCs) are embedded in the nuclear envelope and built from ∼30 different nucleoporins (Nups) in multiple copies, few are integral membrane proteins. One of these transmembrane nucleoporins, Ndc1, is thought to function in NPC assembly at the fused inner and outer nuclear membranes. Here, we show a direct interaction of Ndc1's transmembrane domain with Nup120 and Nup133, members
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Systematic analysis of YFP traps reveals common mRNA/protein discordance in neural tissues. J. Cell Biol. (IF 8.077) Pub Date : 2023-05-05 Joshua S Titlow,Maria Kiourlappou,Ana Palanca,Jeffrey Y Lee,Dalia S Gala,Darragh Ennis,Joyce J S Yu,Florence L Young,David Miguel Susano Pinto,Sam Garforth,Helena S Francis,Finn Strivens,Hugh Mulvey,Alex Dallman-Porter,Staci Thornton,Diana Arman,Marissa J Millard,Aino I Järvelin,Mary Kay Thompson,Martin Sargent,Ilias Kounatidis,Richard M Parton,Stephen Taylor,Ilan Davis
While post-transcriptional control is thought to be required at the periphery of neurons and glia, its extent is unclear. Here, we investigate systematically the spatial distribution and expression of mRNA at single molecule sensitivity and their corresponding proteins of 200 YFP trap lines across the intact Drosophila nervous system. 97.5% of the genes studied showed discordance between the distribution
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Quantitative analysis of autophagy reveals the role of ATG9 and ATG2 in autophagosome formation. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-28 David G Broadbent,Carlo Barnaba,Gloria I Perez,Jens C Schmidt
Autophagy is a catabolic pathway required for the recycling of cytoplasmic materials. To define the mechanisms underlying autophagy it is critical to quantitatively characterize the dynamic behavior of autophagy factors in living cells. Using a panel of cell lines expressing HaloTagged autophagy factors from their endogenous loci, we analyzed the abundance, single-molecule dynamics, and autophagosome
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STED imaging of endogenously tagged ARF GTPases reveals their distinct nanoscale localizations. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-27 Luis Wong-Dilworth,Carmen Rodilla-Ramirez,Eleanor Fox,Steffen D Restel,Alexander Stockhammer,Petia Adarska,Francesca Bottanelli
ADP-ribosylation factor (ARF) GTPases are major regulators of cellular membrane homeostasis. High sequence similarity and multiple, possibly redundant functions of the five human ARFs make investigating their function a challenging task. To shed light on the roles of the different Golgi-localized ARF members in membrane trafficking, we generated CRISPR-Cas9 knockins (KIs) of type I (ARF1 and ARF3)
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Cell cycle controls long-range calcium signaling in the regenerating epidermis. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-27 Jessica L Moore,Dhananjay Bhaskar,Feng Gao,Catherine Matte-Martone,Shuangshuang Du,Elizabeth Lathrop,Smirthy Ganesan,Lin Shao,Rachael Norris,Nil Campamà Sanz,Karl Annusver,Maria Kasper,Andy Cox,Caroline Hendry,Bastian Rieck,Smita Krishnaswamy,Valentina Greco
Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult stem cells signal across regenerative tissue remains unknown due to challenges in studying signaling dynamics in live mice. We combined live imaging in the mouse basal stem cell layer with machine learning tools to analyze patterns of Ca2+ signaling. We show that basal cells
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Human atlastin-3 is a constitutive ER membrane fusion catalyst. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-26 Samantha Bryce,Maureen Stolzer,Daniel Crosby,Ruijin Yang,Dannie Durand,Tina H Lee
Homotypic membrane fusion catalyzed by the atlastin (ATL) GTPase sustains the branched endoplasmic reticulum (ER) network in metazoans. Our recent discovery that two of the three human ATL paralogs (ATL1/2) are C-terminally autoinhibited implied that relief of autoinhibition would be integral to the ATL fusion mechanism. An alternative hypothesis is that the third paralog ATL3 promotes constitutive
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The motor domain of the kinesin Kip2 promotes microtubule polymerization at microtubule tips. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-24 Xiuzhen Chen,Didier Portran,Lukas A Widmer,Marcel M Stangier,Mateusz P Czub,Dimitris Liakopoulos,Jörg Stelling,Michel O Steinmetz,Yves Barral
Kinesins are microtubule-dependent motor proteins, some of which moonlight as microtubule polymerases, such as the yeast protein Kip2. Here, we show that the CLIP-170 ortholog Bik1 stabilizes Kip2 at microtubule ends where the motor domain of Kip2 promotes microtubule polymerization. Live-cell imaging and mathematical estimation of Kip2 dynamics reveal that disrupting the Kip2-Bik1 interaction aborts
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Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-24 Jeffrey M Williams,Yu-Jie Chen,Woo Jung Cho,Andrew W Tai,Billy Tsai
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins
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Expanded directly binds conserved regions of Fat to restrain growth via the Hippo pathway. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-18 Alexander D Fulford,Leonie Enderle,Jannette Rusch,Didier Hodzic,Maxine V Holder,Alex Earl,Robin Hyunseo Oh,Nicolas Tapon,Helen McNeill
The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and
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The IQGAP scaffolds: Critical nodes bridging receptor activation to cellular signaling. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-18 Louise Thines,Francis J Roushar,Andrew C Hedman,David B Sacks
The scaffold protein IQGAP1 assembles multiprotein signaling complexes to influence biological functions. Cell surface receptors, particularly receptor tyrosine kinases and G-protein coupled receptors, are common IQGAP1 binding partners. Interactions with IQGAP1 modulate receptor expression, activation, and/or trafficking. Moreover, IQGAP1 couples extracellular stimuli to intracellular outcomes via
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Cellulose synthase-like D movement in the plasma membrane requires enzymatic activity. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-18 Shu-Zon Wu,Arielle M Chaves,Rongrong Li,Alison W Roberts,Magdalena Bezanilla
Cellulose Synthase-Like D (CSLD) proteins, important for tip growth and cell division, are known to generate β-1,4-glucan. However, whether they are propelled in the membrane as the glucan chains they produce assemble into microfibrils is unknown. To address this, we endogenously tagged all eight CSLDs in Physcomitrium patens and discovered that they all localize to the apex of tip-growing cells and
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Lysosomal chloride transporter CLH-6 protects lysosome membrane integrity via cathepsin activation. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-14 Qianqian Zhang,Yuan Li,Youli Jian,Meijiao Li,Xiaochen Wang
Lysosomal integrity is vital for cell homeostasis, but the underlying mechanisms are poorly understood. Here, we identify CLH-6, the C. elegans ortholog of the lysosomal Cl-/H+ antiporter ClC-7, as an important factor for protecting lysosomal integrity. Loss of CLH-6 affects lysosomal degradation, causing cargo accumulation and membrane rupture. Reducing cargo delivery or increasing CPL-1/cathepsin
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Disagreement among the three musketeers of the unfolded protein response. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-13 András Jipa,Gábor Juhász
Jipa and Juhász preview results from the lab of Tao Wang (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202208147) which show a surprising antagonism between two branches of the unfolded protein response that dictates disease progression in a model of autosomal dominant retinitis pigmentosa.
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Virus update for the M2 "mac-in-touch". J. Cell Biol. (IF 8.077) Pub Date : 2023-04-12 Mojgan H Naghavi
While HIV-1 infection of macrophages plays a major role in viral persistence and pathogenesis, how HIV-1 transfers from infected T cells to macrophages remains elusive. In this issue, Mascarau et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202205103) demonstrate how macrophage polarization drives their ability to fuse with HIV-1 infected T cells via the CD81/RhoA-ROCK/Myosin axis.
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A regulatory circuit comprising the CBP and SIRT7 regulates FAM134B-mediated ER-phagy. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-12 Xinyi Wang,Xiao Jiang,Boran Li,Jiahua Zheng,Jiansheng Guo,Lei Gao,Mengjie Du,Xialian Weng,Lin Li,She Chen,Jingzi Zhang,Lei Fang,Ting Liu,Liang Wang,Wei Liu,Dante Neculai,Qiming Sun
Macroautophagy (autophagy) utilizes a serial of receptors to specifically recognize and degrade autophagy cargoes, including damaged organelles, to maintain cellular homeostasis. Upstream signals spatiotemporally regulate the biological functions of selective autophagy receptors through protein post-translational modifications (PTM) such as phosphorylation. However, it is unclear how acetylation directly
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PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-12 Corbin C Jensen,Amber N Clements,Hope Liou,Lauren E Ball,Jennifer R Bethard,Paul R Langlais,Rachel K Toth,Shailender S Chauhan,Andrea L Casillas,Sohail R Daulat,Andrew S Kraft,Anne E Cress,Cindy K Miranti,Ghassan Mouneimne,Greg C Rogers,Noel A Warfel
Distinguishing key factors that drive the switch from indolent to invasive disease will make a significant impact on guiding the treatment of prostate cancer (PCa) patients. Here, we identify a novel signaling pathway linking hypoxia and PIM1 kinase to the actin cytoskeleton and cell motility. An unbiased proteomic screen identified Abl-interactor 2 (ABI2), an integral member of the wave regulatory
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RFWD3 promotes ZRANB3 recruitment to regulate the remodeling of stalled replication forks. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-10 Chandler E Moore,Selin E Yalcindag,Hanna Czeladko,Ramya Ravindranathan,Yodhara Wijesekara Hanthi,Juliana C Levy,Vincenzo Sannino,Detlev Schindler,Alberto Ciccia,Vincenzo Costanzo,Andrew E H Elia
Replication fork reversal is an important mechanism to protect the stability of stalled forks and thereby preserve genomic integrity. While multiple enzymes have been identified that can remodel forks, their regulation remains poorly understood. Here, we demonstrate that the ubiquitin ligase RFWD3, whose mutation causes Fanconi Anemia, promotes recruitment of the DNA translocase ZRANB3 to stalled replication
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LC3B is a cofactor for LMX1B-mediated transcription of autophagy genes in dopaminergic neurons. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-10 Athanasios Kournoutis,Terje Johansen
It is becoming increasingly clear that the Atg8 family of autophagy proteins have roles not only in the cytoplasm, but also in the cell nucleus. In this issue, Jiménez-Moreno et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.201910133) report that nuclear LC3B binds to the LIM homeodomain transcription factor LMX1B and acts as a cofactor for LMX1B-mediated transcription of autophagy genes, providing
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Mechanosensitive mTORC1 signaling maintains lymphatic valves. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-10 Cansaran Saygili Demir,Amélie Sabine,Muyun Gong,Olivier Dormond,Tatiana V Petrova
Homeostatic maintenance and repair of lymphatic vessels are essential for health. We investigated the dynamics and the molecular mechanisms of lymphatic endothelial cell (LEC) renewal in adult mesenteric quiescent lymphatic vasculature using label-retention, lineage tracing, and cell ablation strategies. Unlike during development, adult LEC turnover and proliferation was confined to the valve regions
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Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-06 Yanan Li,Baijie Xu,Mengmeng Jin,Hui Zhang,Ningxin Ren,Jinhui Hu,Jie He
Correct cell number generation is central to tissue development. However, in vivo roles of coordinated proliferation of individual neural progenitors in regulating cell numbers of developing neural tissues and the underlying molecular mechanism remain mostly elusive. Here, we showed that wild-type (WT) donor retinal progenitor cells (RPCs) generated significantly expanded clones in host retinae with
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PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-06 Ning Zhao,Ning Li,Tao Wang
Chronic endoplasmic reticulum (ER) stress is the underlying cause of many degenerative diseases, including autosomal dominant retinitis pigmentosa (adRP). In adRP, mutant rhodopsins accumulate and cause ER stress. This destabilizes wild-type rhodopsin and triggers photoreceptor cell degeneration. To reveal the mechanisms by which these mutant rhodopsins exert their dominant-negative effects, we established
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Vesicle-associated membrane protein 2 is a cargo-selective v-SNARE for a subset of GPCRs. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-06 Hao Chen,Zara Y Weinberg,G Aditya Kumar,Manojkumar A Puthenveedu
Vesicle fusion at the plasma membrane is critical for releasing hormones and neurotransmitters and for delivering the cognate G protein-coupled receptors (GPCRs) to the cell surface. The SNARE fusion machinery that releases neurotransmitters has been well characterized. In contrast, the fusion machinery that delivers GPCRs is still unknown. Here, using high-speed multichannel imaging to simultaneously
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ATG8-dependent LMX1B-autophagy crosstalk shapes human midbrain dopaminergic neuronal resilience. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-04 Natalia Jiménez-Moreno,Madhu Kollareddy,Petros Stathakos,Joanna J Moss,Zuriñe Antón,Deborah K Shoemark,Richard B Sessions,Ralph Witzgall,Maeve Caldwell,Jon D Lane
The LIM homeodomain transcription factors LMX1A and LMX1B are essential mediators of midbrain dopaminergic neuronal (mDAN) differentiation and survival. Here we show that LMX1A and LMX1B are autophagy transcription factors that provide cellular stress protection. Their suppression dampens the autophagy response, lowers mitochondrial respiration, and elevates mitochondrial ROS, and their inducible overexpression
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RNA recruitment switches the fate of protein condensates from autophagic degradation to accumulation. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-04 Hui Zheng,Kangfu Peng,Xiaomeng Gou,Chen Ju,Hong Zhang
Protein condensates can evade autophagic degradation under stress or pathological conditions. However, the underlying mechanisms are unclear. Here, we demonstrate that RNAs switch the fate of condensates in Caenorhabditis elegans. PGL granules undergo autophagic degradation in embryos laid under normal conditions and accumulate in embryos laid under heat stress conditions to confer stress adaptation
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ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-03 Jing Ze Wu,Mariia Zeziulia,Whijin Kwon,Thomas J Jentsch,Sergio Grinstein,Spencer A Freeman
Degradative organelles contain enzymes that function optimally at the acidic pH generated by the V-ATPase. The resulting transmembrane H+ gradient also energizes the secondary transport of several solutes, including Cl-. We report that Cl- influx, driven by the 2Cl-/H+ exchanger ClC-7, is necessary for the resolution of phagolysosomes formed by macrophages. Cl- transported via ClC-7 had been proposed
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GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3. J. Cell Biol. (IF 8.077) Pub Date : 2023-04-03 Dong Li,Yihong Yang,Chenglin Lv,Yingjie Wang,Xiaoting Chao,Jiafeng Huang,Shashi P Singh,Ye Yuan,Chengyu Zhang,Jizhong Lou,Pu Gao,Shanjin Huang,Bo Li,Huaqing Cai
The actin-rich cortex plays a fundamental role in many cellular processes. Its architecture and molecular composition vary across cell types and physiological states. The full complement of actin assembly factors driving cortex formation and how their activities are spatiotemporally regulated remain to be fully elucidated. Using Dictyostelium as a model for polarized and rapidly migrating cells, we
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Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-30 Hui Liu,Jia-Yi Wei,Yuan Li,Meng Ban,Qi Sun,Hui-Jie Wang,Dan Zhao,Pai-Ge Tong,Li Wang,Kang-Ji Wang,Jin-Li Yue,Hong-Yan Zhang,Wen-Gang Fang,Dong-Xin Liu,De-Shu Shang,Bo Li,Ya-Ping Jin,Liu Cao,Wei-Dong Zhao,Yu-Hua Chen
Microvascular basement membrane (BM) plays a pivotal role in the interactions of astrocyte with endothelium to maintain the blood-brain barrier (BBB) homeostasis; however, the significance and precise regulation of the endothelial cell-derived BM component in the BBB remain incompletely understood. Here, we report that conditional knockout of Atg7 in endothelial cells (Atg7-ECKO) leads to astrocyte-microvascular
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A PI3K-calcium-Nox axis primes leukocyte Nrf2 to boost immune resilience and limit collateral damage. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-30 Giuliana D Clemente,Helen Weavers
Phagosomal reactive oxygen species (ROS) are strategically employed by leukocytes to kill internalized pathogens and degrade cellular debris. Nevertheless, uncontrolled oxidant bursts could cause serious collateral damage to phagocytes or other host tissues, potentially accelerating aging and compromising host viability. Immune cells must, therefore, activate robust self-protective programs to mitigate
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Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-29 Rémi Mascarau,Marie Woottum,Léa Fromont,Rémi Gence,Vincent Cantaloube-Ferrieu,Zoï Vahlas,Kevin Lévêque,Florent Bertrand,Thomas Beunon,Arnaud Métais,Hicham El Costa,Nabila Jabrane-Ferrat,Yohan Gallois,Nicolas Guibert,Jean-Luc Davignon,Gilles Favre,Isabelle Maridonneau-Parini,Renaud Poincloux,Bernard Lagane,Serge Bénichou,Brigitte Raynaud-Messina,Christel Vérollet
Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages
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Yogesh Kulathu: Decoding complex intracellular messages. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-24 Lucia Morgado-Palacin
Yogesh Kulathu studies signaling mechanisms with a focus on ubiquitin and other post-translational modifications such as UFMylation.
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Fine-tune TMEM11 to unleash basal mitophagy. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-17 Thomas G McWilliams
When mitochondrial damage threatens to disrupt cell and tissue homeostasis, selective autophagy (mitophagy) provides an important route to neutralize dysfunctional organelles. Whilst we understand much about stress-induced mitophagy, steady-state and spatial mechanisms remain elusive. In this issue, Gok et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202204021) reveal an unexpected role for
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ADAD2 interacts with RNF17 in P-bodies to repress the Ping-pong cycle in pachytene piRNA biogenesis. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-17 Mengneng Xiong,Lisha Yin,Yiqian Gui,Chunyu Lv,Xixiang Ma,Shuangshuang Guo,Yanqing Wu,Shenglei Feng,Xv Fan,Shumin Zhou,Lingjuan Wang,Yujiao Wen,Xiaoli Wang,Qingzhen Xie,Satoshi H Namekawa,Shuiqiao Yuan
Pachytene piRNA biogenesis is a hallmark of the germline, distinct from another wave of pre-pachytene piRNA biogenesis with regard to the lack of a secondary amplification process known as the Ping-pong cycle. However, the underlying molecular mechanism and the venue for the suppression of the Ping-pong cycle remain elusive. Here, we showed that a testis-specific protein, ADAD2, interacts with a TDRD
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Open Thy Lattice Osteoclast, Resorb me! J. Cell Biol. (IF 8.077) Pub Date : 2023-03-16 Latifa Bakiri
Osteoclasts degrade bone using Cathepsin K and two metalloproteinases: MMP9 and MMP14. In addition to cleaving collagen, Zhu et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202206121) discover that MMP9 and MMP14 also proteolyze galectin-3 on the cell surface. This process drives a galectin-3/LRP1 signaling axis that supports the hard tissue-resorbing function of osteoclasts.
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Cappin' or formin': Formin and capping protein competition for filament ends shapes actin networks. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-16 Vladimir Sirotkin
How cells assemble distinct actin networks from shared cytoplasmic components remains an important unresolved question. In this issue, Wirshing et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202209105) demonstrate how capping protein and formin competition for actin filament barbed ends controls the assembly of branched and linear actin networks.
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ARF3 weights the balance for prostate cancer metastasis. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-15 Patrick T Caswell
Patrick T. Caswell discusses work from Bryant and colleagues (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202206115) which shows how ARF3 impacts metastasis in prostate cancer by regulating a switch between modes of collective invasion.
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A general method for quantitative fractionation of mammalian cells. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-15 Yael Udi,Wenzhu Zhang,Milana E Stein,Inna Ricardo-Lax,Hilda A Pasolli,Brian T Chait,Michael P Rout
Subcellular fractionation in combination with mass spectrometry-based proteomics is a powerful tool to study localization of key proteins in health and disease. Here we offered a reliable and rapid method for mammalian cell fractionation, tuned for such proteomic analyses. This method proves readily applicable to different cell lines in which all the cellular contents are accounted for, while maintaining
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Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface. J. Cell Biol. (IF 8.077) 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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TLN1 contains a cancer-associated cassette exon that alters talin-1 mechanosensitivity. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-06 Lina M Gallego-Paez,William J S Edwards,Manasa Chanduri,Yanyu Guo,Thijs Koorman,Chieh-Yu Lee,Nina Grexa,Patrick Derksen,Jie Yan,Martin A Schwartz,Jan Mauer,Benjamin Thomas Goult
Talin-1 is the core mechanosensitive adapter protein linking integrins to the cytoskeleton. The TLN1 gene is comprised of 57 exons that encode the 2,541 amino acid TLN1 protein. TLN1 was previously considered to be expressed as a single isoform. However, through differential pre-mRNA splicing analysis, we discovered a cancer-enriched, non-annotated 51-nucleotide exon in TLN1 between exons 17 and 18
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A live-cell marker to visualize the dynamics of stable microtubules throughout the cell cycle. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-02 Klara I Jansen,Malina K Iwanski,Mithila Burute,Lukas C Kapitein
The microtubule (MT) cytoskeleton underlies processes such as intracellular transport and cell division. Immunolabeling for posttranslational modifications of tubulin has revealed the presence of different MT subsets, which are believed to differ in stability and function. Whereas dynamic MTs can readily be studied using live-cell plus-end markers, the dynamics of stable MTs have remained obscure due
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Deep learning techniques and mathematical modeling allow 3D analysis of mitotic spindle dynamics. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-02 David Dang,Christoforos Efstathiou,Dijue Sun,Haoran Yue,Nishanth R Sastry,Viji M Draviam
Time-lapse microscopy movies have transformed the study of subcellular dynamics. However, manual analysis of movies can introduce bias and variability, obscuring important insights. While automation can overcome such limitations, spatial and temporal discontinuities in time-lapse movies render methods such as 3D object segmentation and tracking difficult. Here, we present SpinX, a framework for reconstructing
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Proteolytic regulation of a galectin-3/Lrp1 axis controls osteoclast-mediated bone resorption. J. Cell Biol. (IF 8.077) Pub Date : 2023-03-02 Lingxin Zhu,Yi Tang,Xiao-Yan Li,Samuel A Kerk,Costas A Lyssiotis,Xiaoyue Sun,Zijun Wang,Jung-Sun Cho,Jun Ma,Stephen J Weiss
Bone-resorbing osteoclasts mobilize proteolytic enzymes belonging to the matrix metalloproteinase (MMP) family to directly degrade type I collagen, the dominant extracellular matrix component of skeletal tissues. While searching for additional MMP substrates critical to bone resorption, Mmp9/Mmp14 double-knockout (DKO) osteoclasts-as well as MMP-inhibited human osteoclasts-unexpectedly display major
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The small GTPase ARF3 controls invasion modality and metastasis by regulating N-cadherin levels. J. Cell Biol. (IF 8.077) Pub Date : 2023-02-28 Emma Sandilands,Eva C Freckmann,Erin M Cumming,Alvaro Román-Fernández,Lynn McGarry,Jayanthi Anand,Laura Galbraith,Susan Mason,Rachana Patel,Colin Nixon,Jared Cartwright,Hing Y Leung,Karen Blyth,David M Bryant
ARF GTPases are central regulators of membrane trafficking that control local membrane identity and remodeling facilitating vesicle formation. Unraveling their function is complicated by the overlapping association of ARFs with guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and numerous interactors. Through a functional genomic screen of three-dimensional (3D) prostate
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The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA. J. Cell Biol. (IF 8.077) Pub Date : 2023-02-28 Ellis G Jaffray,Michael H Tatham,Barbara Mojsa,Magda Liczmanska,Alejandro Rojas-Fernandez,Yili Yin,Graeme Ball,Ronald T Hay
Acute Promyelocytic Leukemia is caused by expression of the oncogenic Promyelocytic Leukemia (PML)-Retinoic Acid Receptor Alpha (RARA) fusion protein. Therapy with arsenic trioxide results in degradation of PML-RARA and PML and cures the disease. Modification of PML and PML-RARA with SUMO and ubiquitin precedes ubiquitin-mediated proteolysis. To identify additional components of this pathway, we performed
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Antagonism between Prdm16 and Smad4 specifies the trajectory and progression of pancreatic cancer. J. Cell Biol. (IF 8.077) Pub Date : 2023-02-24 Eric Hurwitz,Parash Parajuli,Seval Ozkan,Celine Prunier,Thien Ly Nguyen,Deanna Campbell,Creighton Friend,Allyn Austin Bryan,Ting-Xuan Lu,Steven Christopher Smith,Mohammed Shawkat Razzaque,Keli Xu,Azeddine Atfi
The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-β) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the KrasG12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that
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LGI3/2-ADAM23 interactions cluster Kv1 channels in myelinated axons to regulate refractory period. J. Cell Biol. (IF 8.077) Pub Date : 2023-02-24 Nina Kozar-Gillan,Atanaska Velichkova,George Kanatouris,Yael Eshed-Eisenbach,Gavin Steel,Martine Jaegle,Eerik Aunin,Elior Peles,Carole Torsney,Dies N Meijer
Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon-glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both
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EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in neurons. J. Cell Biol. (IF 8.077) Pub Date : 2023-02-24 Sara S Parker,Kenneth Tran Ly,Adam D Grant,Jillian Sweetland,Ashley M Wang,James D Parker,Mackenzie R Roman,Kathylynn Saboda,Denise J Roe,Megha Padi,Charles W Wolgemuth,Paul Langlais,Ghassan Mouneimne
Dendritic spines are the postsynaptic compartment of a neuronal synapse and are critical for synaptic connectivity and plasticity. A developmental precursor to dendritic spines, dendritic filopodia (DF), facilitate synapse formation by sampling the environment for suitable axon partners during neurodevelopment and learning. Despite the significance of the actin cytoskeleton in driving these dynamic