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  • The Roles of CD8+ T Cell Subsets in Antitumor Immunity
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-07-02
    Michael St. Paul; Pamela S. Ohashi

    Effector CD8+ T cells are typically thought to be a homogenous group of cytotoxic cells that produce interferon-(IFN) γ. However, recent findings have challenged this notion because multiple subsets of CD8+ T cells have been described, each with distinct effector functions and cytotoxic potential. These subsets, referred to as the Tc subsets, have also been detected in tumor microenvironments (TMEs)

  • Conformational Basis of G Protein-Coupled Receptor Signaling Versatility
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-07-02
    Laura M. Wingler; Robert J. Lefkowitz

    G protein-coupled receptors (GPCRs) are privileged structural scaffolds in biology that have the versatility to regulate diverse physiological processes. Interestingly, many GPCR ligands exhibit significant ‘bias’ – the ability to preferentially activate subsets of the many cellular pathways downstream of these receptors. Recently, complementary information from structural and spectroscopic approaches

  • A Novel Paradigm for Expert Core Facility Staff Training
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-07-01
    Jennifer C. Waters

    Scientific research relies on a range of technologies, many of which are developing at a fast pace. Technical experts able to advise researchers on experimental design and validate the performance1 of shared instruments are increasingly recognized as critical members of the research community. Here I describe a novel postdoctoral fellowship program designed to train expert imaging scientists, which

  • Building GLUT4 Vesicles: CHC22 Clathrin’s Human Touch
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-30
    Gwyn W. Gould; Frances M. Brodsky; Nia J. Bryant

    Insulin stimulates glucose transport by triggering regulated delivery of intracellular vesicles containing the GLUT4 glucose transporter to the plasma membrane. This process is defective in diseases such as type 2 diabetes (T2DM). While studies in rodent cells have been invaluable in understanding GLUT4 traffic, evolutionary plasticity must be considered when extrapolating these findings to humans

  • Investigating Cellular Recognition Using CRISPR/Cas9 Genetic Screening
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-25
    Zheng-Shan Chong; Gavin J. Wright; Sumana Sharma

    Neighbouring cells can recognise and communicate with each other by direct binding between cell surface receptor and ligand pairs. Examples of cellular recognition events include pathogen entry into a host cell, sperm–egg fusion, and self/nonself discrimination by the immune system. Despite growing appreciation of cell surface recognition molecules as potential therapeutic targets, identifying key

  • Extracellular Vesicles: New Bullets to Fight Fungal Infections.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-18
    Ramaroson Andriantsitohaina,Nicolas Papon

    While behaving as a commensal yeast in healthy people, Candida albicans remains the deadliest fungal pathogen in immunocompromised patients. Halder et al. deciphered unprecedented immunomodulatory properties of monocyte extracellular vesicles in response to Candida infections, paving the way to consider therapeutic innovations for fungal infections but also inflammatory diseases.

  • Endoplasmic Reticulum (ER) Stress Response Failure in Diseases.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-16
    Kashi Raj Bhattarai,Manoj Chaudhary,Hyung-Ryong Kim,Han-Jung Chae

    Recent work provides evidence for the new terminology, ‘endoplasmic reticulum (ER) stress response or sensing failure’, in relation to metabolic disease. We seek to identify and amass possible conditions of ER stress response failure in various metabolic and age-related pathogenesis, including obesity and diabetes.

  • Regulation and Consequences of cGAS Activation by Self-DNA.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-13
    Christian Zierhut,Hironori Funabiki

    Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a major responder to the pathogenic DNA of viruses and bacteria. Upon DNA binding, cGAS becomes enzymatically active to generate the second messenger cGAMP, leading to activation of inflammatory genes, type I interferon production, autophagy, and cell death. Following genotoxic stress, cGAS can also respond to endogenous DNA, deriving from mitochondria, endogenous

  • Complex Cartography: Regulation of E2F Transcription Factors by Cyclin F and Ubiquitin.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-05
    Michael J Emanuele,Taylor P Enrico,Ryan D Mouery,Danit Wasserman,Sapir Nachum,Amit Tzur

    The E2F family of transcriptional regulators sits at the center of cell cycle gene expression and plays vital roles in normal and cancer cell cycles. Whereas control of E2Fs by the retinoblastoma family of proteins is well established, much less is known about their regulation by ubiquitin pathways. Recent studies placed the Skp1-Cul1-F-box-protein (SCF) family of E3 ubiquitin ligases with the F-box

  • Classical and Nonclassical Intercellular Communication in Senescence and Ageing.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-06-03
    Juan Antonio Fafián-Labora,Ana O'Loghlen

    Intercellular communication refers to the different ways through which cells communicate with each other and transfer a variety of messages. These communication methods involve a number of different processes that occur individually or simultaneously, which change depending on the physiological or pathological context. The best characterized means of intercellular communication is the release of soluble

  • Heterogeneity in mRNA Translation.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-05-25
    Stijn Sonneveld,Bram M P Verhagen,Marvin E Tanenbaum

    During mRNA translation, the genetic information stored in mRNA is translated into a protein sequence. It is imperative that the genetic information is translated with high precision. Surprisingly, however, recent experimental evidence has demonstrated that translation can be highly heterogeneous, even among different mRNA molecules derived from a single gene in an individual cell; multiple different

  • The Centriole Mystique.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-05-23
    Thoru Pederson

    Centrioles organize the microtubule network and mitotic spindle and, as basal bodies, nucleate cilia and flagella. They undergo a beguiling process in which one appears to give rise to another and at a baffling orthogonal geometry. Nucleic acid-based replication has been pondered during cycles of zeniths and nadirs of plausibility, the latter now the state. Centrioles can also arise de novo, and thus

  • Membrane Architecture in the Spotlight of Correlative Microscopy.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-05-10
    Iva Ganeva,Wanda Kukulski

    Cellular membranes differ in their molecular organisation, shape, and dynamics. Knowing how these properties of membrane architecture relate to the presence and function of specific membrane components is fundamental for understanding membrane-associated cellular processes. Correlative light and electron microscopy (CLEM) is ideally poised to address such problems. Fluorescence microscopy allows identification

  • Crowning the Kinetochore: The Fibrous Corona in Chromosome Segregation.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-05-05
    Geert J P L Kops,Reto Gassmann

    The kinetochore is at the heart of chromosome segregation in mitosis and meiosis. Rather than a static linker complex for chromatin and spindle microtubules, it is highly dynamic in composition, size, and shape. While known for decades that it can expand and grow a fibrous meshwork known as the corona, it was until recently unclear what constitutes this 'crown' and what its relevance is for kinetochore

  • Turning the Oxygen Dial: Balancing the Highs and Lows.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-05-05
    Alan H Baik,Isha H Jain

    Oxygen is both vital and toxic to life. Molecular oxygen is the most used substrate in the human body and is required for several hundred diverse biochemical reactions. The discovery of the PHD-HIF-pVHL system revolutionized our fundamental understanding of oxygen sensing and cellular adaptations to hypoxia. It deepened our knowledge of the biochemical underpinnings of numerous diseases, ranging from

  • A Dynamical Paradigm for Molecular Cell Biology.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-30
    John J Tyson,Bela Novak

    The driving passion of molecular cell biologists is to understand the molecular mechanisms that control important aspects of cell physiology, but this ambition is often limited by the wealth of molecular details currently known about these mechanisms. Their complexity overwhelms our intuitive notions of how molecular regulatory networks might respond under normal and stressful conditions. To make progress

  • Metabolic Regulation of Tissue Stem Cells.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-28
    Suzanne N Shapira,Heather R Christofk

    Adult tissue stem cells mediate organ homeostasis and regeneration and thus are continually making decisions about whether to remain quiescent, proliferate, or differentiate into mature cell types. These decisions often integrate external cues, such as energy balance and the nutritional status of the organism. Metabolic substrates and byproducts that regulate epigenetic and signaling pathways are now

  • Fine-Tuning TOM-Mitochondrial Import via Ubiquitin.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-25
    Mohamed A Eldeeb,Andrew N Bayne,Jean-François Trempe,Edward A Fon

    Given their polyvalent functions, an inherent challenge that mitochondria face is the exposure to mitochondrial import stresses, culminating in their dysfunction. Recently, mitochondrial import of several mitochondrial substrates was shown to be regulated via a 'tug of war' between USP30 and MARCH5, two ubiquitin-related enzymes located at the TOM complex.

  • Noncanonical Cell Fate Regulation by Bcl-2 Proteins.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-16
    Stephen Jun Fei Chong,Saverio Marchi,Giulia Petroni,Guido Kroemer,Lorenzo Galluzzi,Shazib Pervaiz

    Bcl-2 proteins are widely known as key controllers of mitochondrial outer membrane permeabilization, arguably the most important step of intrinsic apoptosis. Accumulating evidence indicate that most, if not all, members of the Bcl-2 protein family also mediate a number of apoptosis-unrelated functions. Intriguingly, many of these functions ultimately impinge on cell fate decisions via apoptosis-dependent

  • Structure-Mediated Degradation of CircRNAs.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-15
    Yingli Guo,Xiawei Wei,Yong Peng

    The elaborate control of biogenesis and turnover is essential for circular RNAs (circRNAs) to exert their functions properly in eukaryotic cells, whereas how circRNAs are degraded remains unclear. A recent study by Fischer et al. reveals a novel structure-mediated circRNA decay that selectively degrades highly structured RNAs by UPF1 and G3BP1.

  • The Complex Interplay between Antioxidants and ROS in Cancer.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-14
    Isaac S Harris,Gina M DeNicola

    Reactive oxygen species (ROS) play important roles in tissue homeostasis, cellular signaling, differentiation, and survival. In this review, we discuss the types ofROS, their impact on cellular processes, and their pro- and antitumorigenic effects. Further, we discuss recent advances in our understanding of both endogenous and exogenous antioxidants in tumorigenic processes. Finally, wediscuss how

  • Actin Cell Cortex: Structure and Molecular Organization.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-08
    Tatyana M Svitkina

    The actin cytoskeleton consists of structurally and biochemically different actin filament arrays. Among them, the actin cortex is thought to have key roles in cell mechanics, but remains a poorly characterized part of the actin cytoskeleton. The cell cortex is typically defined as a thin layer of actin meshwork that uniformly underlies the plasma membrane of the entire cell. However, this definition

  • Transcription Factors and DNA Play Hide and Seek.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-07
    David M Suter

    Transcription factors (TFs) bind to specific DNA motifs to regulate the expression of target genes. To reach their binding sites, TFs diffuse in 3D and perform local motions such as 1D sliding, hopping, or intersegmental transfer. TF-DNA interactions depend on multiple parameters, such as the chromatin environment, TF partitioning into distinct subcellular regions, and cooperativity with other DNA-binding

  • Folding the Mitochondrial UPR into the Integrated Stress Response.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-04-02
    Nadine S Anderson,Cole M Haynes

    Eukaryotic cells must accurately monitor the integrity of the mitochondrial network to overcome environmental insults and respond to physiological cues. The mitochondrial unfolded protein response (UPRmt) is a mitochondrial-to-nuclear signaling pathway that maintains mitochondrial proteostasis, mediates signaling between tissues, and regulates organismal aging. Aberrant UPRmt signaling is associated

  • Controlling Cell Death through Post-translational Modifications of DED Proteins.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-29
    Kamil Seyrek,Nikita V Ivanisenko,Max Richter,Laura K Hillert,Corinna König,Inna N Lavrik

    Apoptosis is a form of programmed cell death, deregulation of which occurs in multiple disorders, including neurodegenerative and autoimmune diseases as well as cancer. The formation of a death-inducing signaling complex (DISC) and death effector domain (DED) filaments are critical for initiation of the extrinsic apoptotic pathway. Post-translational modifications (PTMs) of DED-containing DISC components

  • Cholesterol Handling in Lysosomes and Beyond.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-23
    Ying Meng,Saskia Heybrock,Dante Neculai,Paul Saftig

    Lysosomes are of major importance for the regulation of cellular cholesterol homeostasis. Food-derived cholesterol and cholesterol esters contained within lipoproteins are delivered to lysosomes by endocytosis. From the lysosomal lumen, cholesterol is transported to the inner surface of the lysosomal membrane through the glycocalyx; this shuttling requires Niemann-Pick C (NPC) 1 and NPC2 proteins.

  • Emerging Mechanisms and Disease Relevance of Ferroptosis.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-21
    Brent R Stockwell,Xuejun Jiang,Wei Gu

    Cell death is an essential feature of development in multicellular organisms, a critical driver of degenerative diseases, and can be harnessed for treating some cancers. Understanding the mechanisms governing cell death is critical for addressing its role in disease. Similarly, metabolism is essential for normal energy and biomolecule production, and goes awry in many diseases. Metabolism and cell

  • Golgi Apparatus: An Emerging Platform for Innate Immunity.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-21
    Ye Tao,Yanqing Yang,Rongbin Zhou,Tao Gong

    The Golgi apparatus serves as a receiving station where proteins from the endoplasmic reticulum (ER) are further processed before being sent to other cellular compartments. In addition to its well-appreciated roles in vesicular trafficking and protein/lipid secretion, recent studies have demonstrated that the Golgi acts as a signaling platform to facilitate multiple innate immune pathways. Moreover

  • Nitrogen Metabolism in Cancer and Immunity.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-10
    Kiran Kurmi,Marcia C Haigis

    As one of the fundamental requirements for cell growth and proliferation, nitrogen acquisition and utilization must be tightly regulated. Nitrogen can be generated from amino acids (AAs) and utilized for biosynthetic processes through transamination and deamination reactions. Importantly, limitations of nitrogen availability in cells can disrupt the synthesis of proteins, nucleic acids, and other important

  • ER-Phagy: Quality Control and Turnover of Endoplasmic Reticulum.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-03-02
    Haruka Chino,Noboru Mizushima

    The endoplasmic reticulum (ER) is the largest organelle in cells and has fundamental functions, such as folding, processing, and trafficking of proteins, cellular metabolism, and ion storage. To maintain its function, it is turned over constitutively, and even more actively under certain stress conditions. Quality control of the ER is mediated primarily by two pathways: the ubiquitin-proteasome system

  • Multiciliated Cells: Rise and Fall of the Deuterosomes
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-27
    Dheeraj Rayamajhi; Sudipto Roy

    Esoteric organelles called deuterosomes have been implicated in the explosive production of hundreds of basal bodies in multiciliated cells (MCCs). A new study by Meunier, Holland, and colleagues now shows that deuterosomes are dispensable, re-igniting the quest for mechanisms driving basal body biogenesis in this specialized ciliated cell type.

  • Transient Autophagy Inhibition Precipitates Oncogenesis: A Red Flag For Pharmacological Autophagy Inhibitors?
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-27
    Lorenzo Galluzzi,Guido Kroemer

    Recent findings demonstrate that transient genetic inhibition of autophagy promotes age-associated pathologies in mice. While autophagy restoration effectively counteracts such disorders, it also exacerbates the incidence of various solid and hematological tumors. These data may cast additional shadows on the clinical potential of autophagy inhibition for cancer therapy.

  • Structural Insights into STING Signaling.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-24
    Sabrina L Ergun,Lingyin Li

    Since its discovery 12 years ago, the stimulator of interferon genes (STING) pathway has attracted the intense focus of top cell biologists, biochemists, and structural biologists, due to its unique activation mechanisms and broad implications in cancer, aging, and autoimmunity. The STING pathway is an essential innate immune signaling cascade responsible for the sensing of aberrant cytosolic double-stranded

  • Lipid Rafts: Controversies Resolved, Mysteries Remain.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-20
    Ilya Levental,Kandice R Levental,Frederick A Heberle

    The lipid raft hypothesis postulates that lipid-lipid interactions can laterally organize biological membranes into domains of distinct structures, compositions, and functions. This proposal has in equal measure exhilarated and frustrated membrane research for decades. While the physicochemical principles underlying lipid-driven domains has been explored and is well understood, the existence and relevance

  • Poly(ADP-ribose): A Dynamic Trigger for Biomolecular Condensate Formation.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-20
    Anthony K L Leung

    Poly(ADP-ribose) (PAR) is a nucleic acid-like protein modification that can seed the formation of microscopically visible cellular compartments that lack enveloping membranes, recently termed biomolecular condensates. These PAR-mediated condensates are linked to cancer, viral infection, and neurodegeneration. Recent data have shown the therapeutic potential of modulating PAR conjugation (PARylation):

  • Mechanisms Linking Mitochondrial Dysfunction and Proteostasis Failure.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-12
    Bingwei Lu,Su Guo

    Maintaining cellular protein homeostasis (proteostasis) is an essential task for all eukaryotes. Proteostasis failure worsens with aging and is considered a cause of and a therapeutic target for age-related diseases including neurodegenerative disorders. The cellular networks regulating proteostasis and the pathogenic events driving proteostasis failure in disease remain poorly understood. Model organism

  • Mitochondrial Functions in Infection and Immunity
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-11
    Varnesh Tiku; Man-Wah Tan; Ivan Dikic

    Mitochondria have a central role in regulating a range of cellular activities and host responses upon bacterial infection. Multiple pathogens affect mitochondria dynamics and functions to influence their intracellular survival or evade host immunity. On the other side, major host responses elicited against infections are directly dependent on mitochondrial functions, thus placing mitochondria centrally

  • Cell Plasticity in Liver Regeneration
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-11
    Weiping Li; Lu Li; Lijian Hui

    The liver, whose major functional cell type is the hepatocyte, is a peculiar organ with remarkable regenerative capacity. The widely held notion that hepatic progenitor cells contribute to injury-induced liver regeneration has long been debated. However, multiple lines of evidence suggest that the plasticity of differentiated cells is a major mechanism for the cell source in injury-induced liver regeneration

  • CRL4Cdt2: Coupling Genome Stability to Ubiquitination.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-02-07
    Andreas Panagopoulos,Stavros Taraviras,Hideo Nishitani,Zoi Lygerou

    The cullin-RING E3 ubiquitin ligase CRL4Cdt2 has emerged as a master regulator of genome stability, which targets key cell cycle proteins for proteolysis during S phase and after DNA damage. Recent advances shed light on how it couples ubiquitination to DNA synthesis, offering a new paradigm for substrate recognition: Cdt2 binds directly onto proliferating cell nuclear antigen (PCNA) loaded on DNA

  • Getting into Position: Nuclear Movement in Muscle Cells.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-30
    Mafalda Azevedo,Mary K Baylies

    The positioning of nuclei within the cell is a dynamic process that depends on the cell's fate and developmental stage and that is adjusted for optimal cell function. This is especially true in skeletal muscle cells, which contain hundreds of myonuclei distributed evenly along the periphery of the muscle cell. Mispositioned myonuclei are often associated with muscle dysfunction and disease. Different

  • Prime Editing: A New Way for Genome Editing.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-27
    Marek Marzec,Agnieszka Brąszewska-Zalewska,Goetz Hensel

    Precise and efficient use of genome editing tools are hampered by the introduction of DNA double-strand breaks, donor DNA templates, or homology-directed repair. A recent study expands the genome editing toolbox with the introduction of prime editing, which overcomes previous challenges and introduces insertions, deletions, and all putative 12 types of base-to-base conversions in human cells.

  • Subcellular Chemical Imaging: New Avenues in Cell Biology.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-24
    Johan Decelle,Giulia Veronesi,Benoit Gallet,Hryhoriy Stryhanyuk,Pietro Benettoni,Matthias Schmidt,Rémi Tucoulou,Melissa Passarelli,Sylvain Bohic,Peta Clode,Niculina Musat

    To better understand the physiology and acclimation capability of the cell, one of the great challenges of the future is to access the interior of a cell and unveil its chemical landscape (composition and distribution of elements and molecules). Chemical imaging has greatly improved in sensitivity and spatial resolution to visualize and quantify nutrients, metabolites, toxic elements, and drugs in

  • Metabolic Regulation of Cell Fate and Function.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-23
    Shohini Ghosh-Choudhary,Jie Liu,Toren Finkel

    Increasing evidence implicates metabolic pathways as key regulators of cell fate and function. Although the metabolism of glucose, amino acids, and fatty acids is essential to maintain overall energy homeostasis, the choice of a given metabolic pathway and the levels of particular substrates and intermediates increasingly appear to modulate specific cellular activities. This connection is likely related

  • Lipoprotein Lipase Sorting: Sphingomyelin and a Proteoglycan Show the Way.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-22
    Vytas A Bankaitis,Yaxi Wang

    A mechanistic description for how soluble protein cargos are sorted into distinct vesicle classes at the level of the trans-Golgi network (TGN) has remained elusive. In a recent study in Developmental Cell, Sundberg et al. reveal that sphingomyelin and a proteoglycan mediate lipoprotein lipase sorting in the TGN.

  • Viewing Nuclear Architecture through the Eyes of Nocturnal Mammals.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-22
    Yana Feodorova,Martin Falk,Leonid A Mirny,Irina Solovei

    The cell nucleus is a remarkably well-organized organelle with membraneless but distinct compartments of various functions. The largest of them, euchromatin and heterochromatin, are spatially segregated in such a way that the transcriptionally active genome occupies the nuclear interior, whereas silent genomic loci are preferentially associated with the nuclear envelope. This rule is broken by rod

  • Relevance and Regulation of Cell Density.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-21
    Gabriel E Neurohr,Angelika Amon

    Cell density shows very little variation within a given cell type. For example, in humans variability in cell density among cells of a given cell type is 100 times smaller than variation in cell mass. This tight control indicates that maintenance of a cell type-specific cell density is important for cell function. Indeed, pathological conditions such as cellular senescence are accompanied by changes

  • Biogenesis and Functions of Circular RNAs Come into Focus.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-20
    Mei-Sheng Xiao,Yuxi Ai,Jeremy E Wilusz

    Many eukaryotic protein-coding genes are able to generate exonic circular RNAs. Most of these covalently linked transcripts are expressed at low levels, but some accumulate to higher levels than their associated linear mRNAs. We highlight several methodologies that have been developed in recent years to identify and characterize these transcripts, and which have revealed an increasingly detailed view

  • How the Mitoprotein-Induced Stress Response Safeguards the Cytosol: A Unified View.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-18
    Felix Boos,Johnathan Labbadia,Johannes M Herrmann

    Mitochondrial and cytosolic proteostasis are of central relevance for cellular stress resistance and organismal health. Recently, a number of individual cellular programs were described that counter the fatal consequences of mitochondrial dysfunction. These programs remove arrested import intermediates from mitochondrial protein translocases, stabilize protein homeostasis within mitochondria, and,

  • RIPK1 Kinase-Dependent Death: A Symphony of Phosphorylation Events.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-17
    Tom Delanghe,Yves Dondelinger,Mathieu J M Bertrand

    The serine/threonine kinase RIPK1 has emerged as a crucial component of the inflammatory response activated downstream of several immune receptors, where it paradoxically functions as a scaffold to protect the cell from death or instead as an active kinase to promote the killing of the cell. While RIPK1 kinase-dependent cell death has revealed its physiological importance in the context of microbial

  • When Separation Strengthens Ties.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-15
    Helena Canever,François Sipieter,Nicolas Borghi

    Phase separation underlies functional compartmentalization in living systems. Two recent studies (Beutel et al. and Schwayer et al.) show that zonula occludens (ZO) proteins of tight junctions (TJs) condense into compartments within the cytoplasm that display liquid properties. This ability to condense predicts normal TJ assembly and epithelial barrier function which are essential for vertebrate embryogenesis

  • Protecting the Aging Genome.
    Trends Cell Biol. (IF 16.041) Pub Date : 2020-01-06
    Michael A Petr,Tulika Tulika,Lina M Carmona-Marin,Morten Scheibye-Knudsen

    Mounting evidence suggests that DNA damage plays a central role in aging. Multiple tiers of defense have evolved to reduce the accumulation of DNA damage, including reducing damaging molecules, repairing DNA damage, and inducing senescence or apoptosis in response to persistent DNA damage. Mutations in or failure of these pathways can lead to accelerated or premature aging and age-related decline in

  • Organoid and Assembloid Technologies for Investigating Cellular Crosstalk in Human Brain Development and Disease.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-23
    Rebecca M Marton,Sergiu P Pașca

    The biology of the human brain, and in particular the dynamic interactions between the numerous cell types and regions of the central nervous system, has been difficult to study due to limited access to functional brain tissue. Technologies to derive brain organoids and assembloids from human pluripotent stem cells are increasingly utilized to model, in progressively complex preparations, the crosstalk

  • Epigenetic Regulation of Mesenchymal Stem Cell Homeostasis.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-20
    Bing-Dong Sui,Chen-Xi Zheng,Meng Li,Yan Jin,Cheng-Hu Hu

    Mesenchymal stem cells (MSCs) have putative roles in maintaining adult tissue health, and the functional decline of MSCs has emerged as a crucial pathophysiological driver of various diseases. Epigenetic regulation is essential for establishing and preserving MSC homeostasis in vivo. Furthermore, growing evidence suggests that epigenetic dysregulation contributes to age- and disease-associated MSC

  • Mobility and Repair of Damaged DNA: Random or Directed?
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-10
    Roxanne Oshidari,Karim Mekhail,Andrew Seeber

    The increased mobility of damaged DNA within the nucleus can promote genome stability and cell survival. New cell biology approaches have indicated that damaged DNA mobility exhibits random and directed movements during DNA repair. Here, we review recent studies that collectively reveal that cooperation between different molecular mechanisms, which underlie increases in the random and directional motion

  • Squeezing in a Meal: Myosin Functions in Phagocytosis.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-10
    Sarah R Barger,Nils C Gauthier,Mira Krendel

    Phagocytosis is a receptor-mediated, actin-dependent process of internalization of large extracellular particles, such as pathogens or apoptotic cells. Engulfment of phagocytic targets requires the activity of myosins, actin-dependent molecular motors, which perform a variety of functions at distinct steps during phagocytosis. By applying force to actin filaments, the plasma membrane, and intracellular

  • Coupling DNA Damage and Repair: an Essential Safeguard during Programmed DNA Double-Strand Breaks?
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-06
    Mireille Bétermier,Valérie Borde,Jean-Pierre de Villartay

    DNA double-strand breaks (DSBs) are the most toxic DNA lesions given their oncogenic potential. Nevertheless, programmed DSBs (prDSBs) contribute to several biological processes. Formation of prDSBs is the 'price to pay' to achieve these essential biological functions. Generated by domesticated PiggyBac transposases, prDSBs have been integrated in the life cycle of ciliates. Created by Spo11 during

  • Splicing Busts a Move: Isoform Switching Regulates Migration.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-03
    Mithun Mitra,Ha Neul Lee,Hilary A Coller

    Cell migration is essential for normal development, neural patterning, pathogen eradication, and cancer metastasis. Pre-mRNA processing events such as alternative splicing and alternative polyadenylation result in greater transcript and protein diversity as well as function and activity. A critical role for alternative pre-mRNA processing in cell migration has emerged in axon outgrowth during neuronal

  • The Hippo Pathway, YAP/TAZ, and the Plasma Membrane.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-12-02
    Valentina Rausch,Carsten G Hansen

    The plasma membrane allows the cell to sense and adapt to changes in the extracellular environment by relaying external inputs via intracellular signaling networks. One central cellular signaling pathway is the Hippo pathway, which regulates homeostasis and plays chief roles in carcinogenesis and regenerative processes. Recent studies have found that mechanical stimuli and diffusible chemical components

  • Nicotinamide Nucleotide Transhydrogenase as a Sensor of Mitochondrial Biology.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-11-18
    Salvatore Nesci,Fabiana Trombetti,Alessandra Pagliarani

    The enzyme nicotinamide nucleotide transhydrogenase (NNT) transfers hydride from NADH to NADP+ coupled to H+ translocation across the inner mitochondrial membrane. In a recent study, Kampjut and Sazanov reveal that the bifunctional NNT mechanism rules the NAD(P)+/NAD(P)H interconversion ratio, which in turn regulates antioxidant defense and sirtuin actions.

  • Mechanisms for Active Regulation of Biomolecular Condensates.
    Trends Cell Biol. (IF 16.041) Pub Date : 2019-11-18
    Johannes Söding,David Zwicker,Salma Sohrabi-Jahromi,Marc Boehning,Jan Kirschbaum

    Liquid-liquid phase separation is a key organizational principle in eukaryotic cells, on par with intracellular membranes. It allows cells to concentrate specific proteins into condensates, increasing reaction rates and achieving switch-like regulation. We propose two active mechanisms that can explain how cells regulate condensate formation and size. In both, the cell regulates the activity of an

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