Ubiquitylation: How Nucleosomes Use Histones to Evict Histones.
Abstract Steric hindrances by bulky histone modifications (such as ubiquitylation) could destabilize and remodel canonical nucleosome structure. This highlights a novel mechanism by which bulky modifications directly regulate chromatin, distinct from the more generally accepted roles of histone modifications in the recruitment of downstream effectors and histone charge shielding. PMID: 31277892 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - July 2, 2019 Category: Cytology Authors: Krajewski WA Tags: Trends Cell Biol Source Type: research

Quiescence: Good and Bad of Stem Cell Aging.
KL Abstract Stem cells are required for lifelong homeostasis and regeneration of tissues and organs in mammals, but the function of stem cells declines during aging. To preserve stem cells during life, they are kept in a quiescent state with low metabolic and low proliferative activity. However, activation of quiescent stem cells - an essential process for organ homeostasis/regeneration - requires concerted and faithful regulation of multiple molecular circuits controlling biosynthetic processes, repair mechanisms, and metabolic activity. Thus, while protecting stem cell maintenance, quiescence comes at the cost ...
Source: Trends in Cell Biology - June 24, 2019 Category: Cytology Authors: Tümpel S, Rudolph KL Tags: Trends Cell Biol Source Type: research

Dissecting Gene Repression: Not Just Location, Location, Location.
Abstract Large heterochromatic domains are found tethered to the lamina. But, is this nuclear environment repressive per se, or just the 'ground state' of inactive chromatin? Elegant studies from the van Steensel group (Leemans et al., Cell, 2019) recently demonstrated that the lamina is indeed repressive, but that intrinsic promoter properties also dictate gene activity. PMID: 31235204 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - June 21, 2019 Category: Cytology Authors: Sexton T Tags: Trends Cell Biol Source Type: research

Mitotic Chromosome Mechanics: How Cells Segregate Their Genome.
Abstract During mitosis, replicated chromosomes segregate such that each daughter cell receives one copy of the genome. Faithful mechanical transport during mitosis requires that chromosomes undergo extensive structural changes as the cell cycle progresses, resulting in the formation of compact, cylindrical bodies. Such structural changes encompass a range of different activities, including longitudinal condensation of the chromosome axis, global chromatin compaction, resolution of sister chromatids, and individualisation of chromosomes into separate bodies. After mitosis, chromosomes undergo further reorganisatio...
Source: Trends in Cell Biology - June 20, 2019 Category: Cytology Authors: Batty P, Gerlich DW Tags: Trends Cell Biol Source Type: research

Chasing Uptake: Super-Resolution Microscopy in Endocytosis and Phagocytosis.
Abstract Since their invention about two decades ago, super-resolution microscopes have become a method of choice in cell biology. Owing to a spatial resolution below 50 nm, smaller than the size of most organelles, and an order of magnitude better than the diffraction limit of conventional light microscopes, super-resolution microscopy is a powerful technique for resolving intracellular trafficking. In this review we discuss discoveries in endocytosis and phagocytosis that have been made possible by super-resolution microscopy - from uptake at the plasma membrane, endocytic coat formation, and cytoskeletal rearra...
Source: Trends in Cell Biology - June 18, 2019 Category: Cytology Authors: Baranov MV, Olea RA, van den Bogaart G Tags: Trends Cell Biol Source Type: research

Membrane Trafficking Decisions Regulate Primary Cilium Formation.
Abstract Rab11 and its interacting partners play a crucial role in primary cilia assembly in mammalian cells. A recent study (Walia et al., Dev. Cell, 2019) describes an as yet unexplored role for one of the Rab11 binding proteins, WDR44, in negatively regulating ciliary trafficking in concert with Akt. PMID: 31221497 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - June 17, 2019 Category: Cytology Authors: Goldenring JR Tags: Trends Cell Biol Source Type: research

The Complexity of PRC2 Subcomplexes.
Abstract Polycomb repressive complex 2 (PRC2) is a multisubunit protein complex essential for the development of multicellular organisms. Recruitment of PRC2 to target genes, followed by deposition and propagation of its catalytic product histone H3 lysine 27 trimethylation (H3K27me3), are key to the spatiotemporal control of developmental gene expression. Recent breakthrough studies have uncovered unexpected roles for substoichiometric PRC2 subunits in these processes. Here, we elaborate on how the facultative PRC2 subunits regulate catalytic activity, locus-specific PRC2 binding, and propagation of H3K27me3, and...
Source: Trends in Cell Biology - June 6, 2019 Category: Cytology Authors: van Mierlo G, Veenstra GJC, Vermeulen M, Marks H Tags: Trends Cell Biol Source Type: research

Nucleolus: A Central Hub for Nuclear Functions.
Abstract The nucleolus is the largest and most studied nuclear body, but its role in nuclear function is far from being comprehensively understood. Much work on the nucleolus has focused on its role in regulating RNA polymerase I (RNA Pol I) transcription and ribosome biogenesis; however, emerging evidence points to the nucleolus as an organizing hub for many nuclear functions, accomplished via the shuttling of proteins and nucleic acids between the nucleolus and nucleoplasm. Here, we discuss the cellular mechanisms affected by shuttling of nucleolar components, including the 3D organization of the genome, stress ...
Source: Trends in Cell Biology - June 5, 2019 Category: Cytology Authors: Iarovaia OV, Minina EP, Sheval EV, Onichtchouk D, Dokudovskaya S, Razin SV, Vassetzky YS Tags: Trends Cell Biol Source Type: research

Lysosome Fission: Planning for an Exit.
Abstract Lysosomes are acidic and degradative organelles that receive and digest a plethora of molecular and particulate cargo delivered by endocytosis, autophagy, and phagocytosis. The mechanisms responsible for sorting, transporting, and ultimately delivering membranes and cargo to lysosomes through fusion have been intensely investigated. Much less is understood about lysosome fission, which is necessary to balance the incessant flow of cargo into lysosomes and maintain steady-state number, size, and function of lysosomes. Here, we review the emerging picture of how lipid signals, coat and adaptor proteins, and...
Source: Trends in Cell Biology - June 3, 2019 Category: Cytology Authors: Saffi GT, Botelho RJ Tags: Trends Cell Biol Source Type: research

Acetate Metabolism in Physiology, Cancer, and Beyond.
Abstract Acetate and the related metabolism of acetyl-coenzyme A (acetyl-CoA) confer numerous metabolic functions, including energy production, lipid synthesis, and protein acetylation. Despite its importance as a nutrient for cellular metabolism, its source has been unclear. Recent studies have provided evidence to support the existence of a de novo pathway for acetate production derived from pyruvate, the end product of glycolysis. This mechanism of pyruvate-derived acetate generation could have far-reaching implications for the regulation of central carbon metabolism. In this Opinion, we discuss our current und...
Source: Trends in Cell Biology - May 31, 2019 Category: Cytology Authors: Bose S, Ramesh V, Locasale JW Tags: Trends Cell Biol Source Type: research

Cellular Reprogramming as a Therapeutic Target in Cancer.
Abstract Cancer heterogeneity has long been recognized as an important clinical determinant of patient outcomes and, thus, many new cancer treatments have been designed to target these different cells. Despite the short-term achievements of current therapies, including chemotherapy, antiangiogenesis therapy, radiotherapy, and immunotherapy, the long-term success of cancer regression remains poor. Therefore, researchers have investigated a new property, cellular reprogramming, in cancer that not only contributes to the classic hallmarks of cancer, but also suggests that cancer is a dynamic event rather than a stati...
Source: Trends in Cell Biology - May 29, 2019 Category: Cytology Authors: Xiong S, Feng Y, Cheng L Tags: Trends Cell Biol Source Type: research

Oxysterol Binding Protein: Tether, Transporter … and Flux Capacitor?
Oxysterol Binding Protein: Tether, Transporter… and Flux Capacitor? Trends Cell Biol. 2019 May 15;: Authors: Hammond GRV, Pacheco J Abstract The oxysterol binding protein (OSBP) is a storied protein in organelle biology. Its early roles include acting as a membrane contact site (MCS) tether as well as a lipid antiporter. A surprising new function for OSBP in MCS dynamics has now been uncovered in a recent study by Jamecna et al. (Dev. Cell 2019;49:220-234). PMID: 31103279 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - May 15, 2019 Category: Cytology Authors: Hammond GRV, Pacheco J Tags: Trends Cell Biol Source Type: research

Probing Mechanical Properties in Biology Using Brillouin Microscopy.
Abstract Brillouin microscopy can be used to map the mechanical properties of samples in a noncontact and label-free manner, with potential applications in cell biology. Here, we provide an overview of the underlying principles and technology as well as the current challenges and outlook. PMID: 31085065 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - May 10, 2019 Category: Cytology Authors: Elsayad K, Polakova S, Gregan J Tags: Trends Cell Biol Source Type: research

Phase Separation and the Centrosome: A Fait Accompli?
Abstract There is currently intense interest in the idea that many membraneless organelles might assemble through phase separation of their constituent molecules into biomolecular 'condensates' that have liquid-like properties. This idea is intuitively appealing, especially for complex organelles such as centrosomes, where a liquid-like structure would allow the many constituent molecules to diffuse and interact with one another efficiently. I discuss here recent studies that either support the concept of a liquid-like centrosome or suggest that centrosomes are assembled upon a more solid, stable scaffold. I sugge...
Source: Trends in Cell Biology - May 7, 2019 Category: Cytology Authors: Raff JW Tags: Trends Cell Biol Source Type: research

The Epigenetics of Stem Cell Aging Comes of Age.
Abstract Emerging evidence indicates that epigenetic regulators are critically required for the maintenance of tissue-specific stem cells and that the epigenetic marks are altered in stem cells during physiological aging. Intriguingly, aging-associated stem cell functional decline can be reversed by manipulating epigenetic factors that become dysregulated during aging. These observations lend support to the stem cell theory of aging, which postulates that aging is the result of the inability of tissue-specific stem cells to replenish the tissues with functional differentiated cells that maintain the function of a ...
Source: Trends in Cell Biology - April 25, 2019 Category: Cytology Authors: Chen D, Kerr C Tags: Trends Cell Biol Source Type: research

Versatility of Preprotein Transfer from the Cytosol to Mitochondria.
Abstract Mitochondrial biogenesis requires the import of a large number of precursor proteins from the cytosol. Although specific membrane-bound preprotein translocases have been characterized in detail, it was assumed that protein transfer from the cytosol to mitochondria mainly involved unselective binding to molecular chaperones. Recent findings suggest an unexpected versatility of protein transfer to mitochondria. Cytosolic factors have been identified that bind to selected subsets of preproteins and guide them to mitochondrial receptors in a post-translational manner. Cotranslational import processes are emer...
Source: Trends in Cell Biology - April 25, 2019 Category: Cytology Authors: Becker T, Song J, Pfanner N Tags: Trends Cell Biol Source Type: research

Molecular Comprehension of Mcl-1: From Gene Structure to Cancer Therapy.
Abstract Among cell death regulators, members of the Bcl-2 family are of interest because they are highly conserved across species and represent promising targets for anticancer therapy. This family and its associated proteins include more than 25 members, with either anti- or proapoptotic functions. Although the overall regulation of apoptosis by Bcl-2 family proteins is now well understood, targeted therapy requires careful consideration of individual members of the family and their crosstalk. One of the most studied representatives of the Bcl-2 family is antiapoptotic Mcl-1. After 25 years of investigations, a ...
Source: Trends in Cell Biology - April 25, 2019 Category: Cytology Authors: Senichkin VV, Streletskaia AY, Zhivotovsky B, Kopeina GS Tags: Trends Cell Biol Source Type: research

APC/C Ubiquitin Ligase: Coupling Cellular Differentiation to G1/G0 Phase in Multicellular Systems.
Abstract The anaphase-promoting complex/cyclosome (APC/C) is an evolutionarily conserved ubiquitin ligase that controls cell cycle progression through spatiotemporally regulated proteolysis. Although recent studies revealed its postmitotic function, our knowledge of the role of APC/C beyond cell cycle regulation in the biology of multicellular organisms is far from complete. Here, I review recent advances in the function of APC/C in animal development, specifically focusing on its emerging role in regulating cell differentiation. I describe how APC/C regulates distinct processes during the course of differentiatio...
Source: Trends in Cell Biology - April 15, 2019 Category: Cytology Authors: Kimata Y Tags: Trends Cell Biol Source Type: research

Intratumoral Heterogeneity: More Than Just Mutations.
Abstract Most human tumors are composed of genetically and phenotypically heterogeneous cancer cell populations, which poses a major challenge for the clinical management of cancer patients. Advances of single-cell technologies have allowed the profiling of tumors at unprecedented depth, which, in combination with newly developed computational tools, enable the dissection of tumor evolution with increasing precision. However, our understanding of mechanisms that regulate intratumoral heterogeneity and our ability to modulate it has been lagging behind. Recent data demonstrate that epigenetic regulators, including ...
Source: Trends in Cell Biology - April 12, 2019 Category: Cytology Authors: Hinohara K, Polyak K Tags: Trends Cell Biol Source Type: research

Phosphoinositides Break Microtubule Dynamics Symmetry in the Phragmoplast.
Abstract Plant cytokinesis rely on asymmetric behavior of microtubules: bulk polymerization at the phragmoplast leading zone and bulk depolymerization at the phragmoplast lagging zone. Recent findings demonstrate that phosphatidylinositol 4-kinase beta (PI4Kβ) plays an essential role in this asymmetry by facilitating the establishment of the phragmoplast lagging zone. PMID: 30962043 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - April 5, 2019 Category: Cytology Authors: Smertenko A Tags: Trends Cell Biol Source Type: research

Cancer Cells Thrive on Stress.
Abstract Glucocorticoids (GCs) are widely used for the management of disease- or therapy-related complications in cancer patients. Recent data indicate that activation of GC receptors (GRs) precipitates breast cancer progression by favoring metastatic dissemination and cell survival at distant sites. These findings call for the re-evaluation of GC usage in patients with cancer. PMID: 30962044 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - April 5, 2019 Category: Cytology Authors: Galluzzi L, Kroemer G Tags: Trends Cell Biol Source Type: research

Nuclear Actin and Actin-Binding Proteins in DNA Repair.
Abstract Nuclear actin has been implicated in a variety of DNA-related processes including chromatin remodeling, transcription, replication, and DNA repair. However, the mechanistic understanding of actin in these processes has been limited, largely due to a lack of research tools that address the roles of nuclear actin specifically, that is, distinct from its cytoplasmic functions. Recent findings support a model for homology-directed DNA double-strand break (DSB) repair in which a complex of ARP2 and ARP3 (actin-binding proteins 2 and 3) binds at the break and works with actin to promote DSB clustering and homol...
Source: Trends in Cell Biology - April 3, 2019 Category: Cytology Authors: Hurst V, Shimada K, Gasser SM Tags: Trends Cell Biol Source Type: research

Regulation of Gene Expression by N6-methyladenosine in Cancer.
Abstract As the most abundant mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) has recently emerged as an important regulator of gene expression. m6A modification can be deposited by m6A methyltransferases, removed by m6A demethylases, and recognized by different reader proteins. Numerous lines of evidence have shown that m6A methylation plays critical roles regulating gene expression in development and disease. In this review, we summarize the molecular and cellular function of m6A and highlight some key results which demonstrate the role of m6A in various cancers. Finally, we discuss future direct...
Source: Trends in Cell Biology - March 30, 2019 Category: Cytology Authors: Liu J, Harada BT, He C Tags: Trends Cell Biol Source Type: research

Tau: It's Not What You Think.
Abstract Tau is a multifunctional microtubule-associated protein in the neuron. For decades, tau's main function in neurons has been broadly accepted as stabilizing microtubules in the axon; however, this conclusion was reached mainly on the basis of studies performed in vitro and on ectopic expression of tau in non-neuronal cells. The idea has become so prevailing that some disease researchers are even seeking to use microtubule-stabilizing drugs to treat diseases in which tau dissociates from microtubules. Recent work suggests that tau is not a stabilizer of microtubules in the axon, but rather enables axonal mi...
Source: Trends in Cell Biology - March 28, 2019 Category: Cytology Authors: Baas PW, Qiang L Tags: Trends Cell Biol Source Type: research

The Expanding and Unexpected Functions of Mitochondria Contact Sites.
Abstract Mitochondria make functionally relevant contacts with most, if not all, other organelles in the cell. These contacts impact on mitochondrial behavior and function as well as on a wide variety of cellular functions. Many recent advances have been made in the rapidly growing field of mitochondria contact site biology, and these advances have expanded the known functions of mitochondria contact sites in exciting and unexpected ways. PMID: 30929794 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - March 28, 2019 Category: Cytology Authors: Lackner LL Tags: Trends Cell Biol Source Type: research

Multidimensional Single-Cell Analyses in Organ Development and Maintenance.
Abstract The revolution of single-cell analysis tools in epigenomics, transcriptomics, lineage tracing, and transcriptome-scale RNA imaging, has boosted our understanding of the underlying molecular mechanisms during organ development and maintenance. Application of these tools enables the multidimensional study of organs, from cell atlas profiling, spatial organization, to cell-cell interaction. Here, we discuss recent progress in employing multidimensional single-cell analyses to address fundamental questions related to the development and maintenance of hematopoietic organs, brain and lung, which will also help...
Source: Trends in Cell Biology - March 27, 2019 Category: Cytology Authors: Zhang Y, Liu F Tags: Trends Cell Biol Source Type: research

Regulation and Function of Mitochondria-Lysosome Membrane Contact Sites in Cellular Homeostasis.
Abstract Mitochondrial and lysosomal function are intricately related and critical for maintaining cellular homeostasis, as highlighted by multiple diseases linked to dysfunction of both organelles. Recent work using high-resolution microscopy demonstrates the dynamic formation of inter-organelle membrane contact sites between mitochondria and lysosomes, allowing for their direct interaction in a pathway distinct from mitophagy or lysosomal degradation of mitochondrial-derived vesicles. Mitochondria-lysosome contact site tethering is mechanistically regulated by mitochondrial proteins promoting Rab7 GTP hydrolysis...
Source: Trends in Cell Biology - March 18, 2019 Category: Cytology Authors: Wong YC, Kim S, Peng W, Krainc D Tags: Trends Cell Biol Source Type: research

Dispatching Sonic Hedgehog: Molecular Mechanisms Controlling Deployment.
Abstract The Hedgehog (Hh) family of morphogens direct cell fate decisions during embryogenesis and signal to maintain tissue homeostasis after birth. Hh ligands harbor dual lipid modifications that anchor the proteins into producing cell membranes, effectively preventing ligand release. The transporter-like protein Dispatched (Disp) functions to release these membrane tethers and mobilize Hh ligands to travel toward distant cellular targets. The molecular mechanisms by which Disp achieves Hh deployment are not yet fully understood, but a number of recent publications provide insight into the complex process of Hh...
Source: Trends in Cell Biology - March 6, 2019 Category: Cytology Authors: Hall ET, Cleverdon ER, Ogden SK Tags: Trends Cell Biol Source Type: research

Activated Extracellular Vesicles as New Therapeutic Targets?
Abstract A recent study by Genschmer et al. (Cell 2019;176:113-126) presents provocative new evidence that extracellular vesicles/exosomes released by activated neutrophils can degrade extracellular proteins. Elastase that is produced by neutrophils both coats the exosomes and is protected by the exosomes from inactivation by α1 antitrypsin, ultimately causing the pathological degradation of extracellular protein fibrils in lung alveoli. PMID: 30826213 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - February 27, 2019 Category: Cytology Authors: Languino LR, Hooper DC Tags: Trends Cell Biol Source Type: research

The Role of EMC during Membrane Protein Biogenesis.
Abstract Ten years ago, high-throughput genetic interaction analyses revealed an abundant and widely conserved protein complex residing in the endoplasmic reticulum (ER) membrane. Dubbed the ER membrane protein complex (EMC), its disruption has since been found to affect wide-ranging processes, including protein trafficking, organelle communication, ER stress, viral maturation, lipid homeostasis, and others. However, its molecular function has remained enigmatic. Recent studies suggest a role for EMC during membrane protein biogenesis. Biochemical reconstitution experiments show that EMC can directly mediate the i...
Source: Trends in Cell Biology - February 27, 2019 Category: Cytology Authors: Chitwood PJ, Hegde RS Tags: Trends Cell Biol Source Type: research

Fibroblasts Prompt Tumors to Mobilize Their Glycogen Reserves.
Abstract Cancer cells use multiple strategies to fuel their unchecked growth. Inarecent paper, Curtis etal.(CellMetab. 2019;29:141-155) delineate a novel strategy whereby cancer-associated fibroblasts (CAFs) secrete cytokines that stimulate glycogen breakdown in ovarian cancer cells. CAF-induced glycogen breakdown increases glycolysis and ATP generation, and facilitates proliferation and metastasis. PMID: 30826215 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - February 27, 2019 Category: Cytology Authors: Coller HA Tags: Trends Cell Biol Source Type: research

Phase Separation, Transition, and Autophagic Degradation of Proteins in Development and Pathogenesis.
Abstract Phase separation and transition control the assembly and material states (liquid, gel like, or solid) of protein condensates to ensure that distinct cellular functions occur in a spatiotemporally controlled manner. The assembly and biophysical properties of condensates are precisely regulated by chaperone proteins, post-translational modifications (PTMs), and numerous cellular factors. Phase separation also triages misfolded and unwanted proteins for autophagic degradation. The concerted actions of receptor proteins, scaffold proteins, and PTMs determine the size, assembly rate, and material properties of...
Source: Trends in Cell Biology - February 27, 2019 Category: Cytology Authors: Wang Z, Zhang H Tags: Trends Cell Biol Source Type: research

Metastasis Stemming from Circulating Tumor Cell Clusters.
Abstract Circulating tumor cell (CTC) clusters have an enhanced capacity to initiate metastases, compared with single cells, but it is unclear how they gain such advantage. A recent study by Gkountela et al. (Cell 2019;176:98-112) links the physical state of clusters with increased accessibility of stem cell-related transcription factors, providing novel insights into the epigenetic regulation of 'stemness' in CTC clusters. PMID: 30799250 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - February 21, 2019 Category: Cytology Authors: Yu M Tags: Trends Cell Biol Source Type: research

Paracrine Mechanisms of Redox Signalling for Postmitotic Cell and Tissue Regeneration.
Abstract Adult postmitotic mammalian cells, including neurons and cardiomyocytes, have a limited capacity to regenerate after injury. Therefore, an understanding of the molecular mechanisms underlying their regenerative ability is critical to advance tissue repair therapies. Recent studies highlight how redox signalling via paracrine cell-to-cell communication may act as a central mechanism coupling tissue injury with regeneration. Post-injury redox paracrine signalling can act by diffusion to nearby cells, through mitochondria or within extracellular vesicles, affecting specific intracellular targets such as kina...
Source: Trends in Cell Biology - February 19, 2019 Category: Cytology Authors: Hervera A, Santos CX, De Virgiliis F, Shah AM, Di Giovanni S Tags: Trends Cell Biol Source Type: research

Mutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy.
Abstract Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies. Here, we explore how tumor-intrinsic factors...
Source: Trends in Cell Biology - February 11, 2019 Category: Cytology Authors: Vitale I, Sistigu A, Manic G, Rudqvist NP, Trajanoski Z, Galluzzi L Tags: Trends Cell Biol Source Type: research

Towards the Mechanism of Yeast Telomere Dynamics.
Abstract A mechanistic understanding of the yeast telomere requires an integrated understanding of telomere chromatin structure (telosomes), telomeric origins of replications, telomere length homeostasis, and telosome epigenetics. Recent molecular and genetic studies of the yeast telosomal components Rap1, Rif1, and Rif2, the Mre11 complex, and Tel1ATM promise to increase our insight into the coordination between these processes. Here, an intricate relationship is proposed between these multiple components that has resulted in increased appreciation of the multiple levels of telomere length control and their diffe...
Source: Trends in Cell Biology - February 11, 2019 Category: Cytology Authors: Lustig AJ Tags: Trends Cell Biol Source Type: research

Biology of RNA Surveillance in Development and Disease.
Abstract The 'RNA world', in which RNA molecules stored information and acquired enzymatic properties, has been proposed to have preceded organism life. RNA is now recognized for its central role in biology, with accumulating evidence implicating coding and noncoding (nc)RNAs in myriad mechanisms regulating cellular physiology and disequilibrium in transcriptomes resulting in pathological conditions. Nascently synthesized RNAs are subjected to stringent regulation by sophisticated RNA surveillance pathways. In this review, we integrate these pathways from a developmental viewpoint, proposing RNA surveillance as th...
Source: Trends in Cell Biology - February 9, 2019 Category: Cytology Authors: Laffleur B, Basu U Tags: Trends Cell Biol Source Type: research

Class II PI3K Functions in Cell Biology and Disease.
Abstract The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate inositol phospholipids, thereby controlling membrane lipid composition and regulating a wide range of intracellular processes, including vesicular trafficking and signal transduction. Despite the vast knowledge on class I PI3Ks, recent studies are only now revealing the importance of class II PI3Ks in cell proliferation, survival, and migration. Increasing evidence suggests that the three class II PI3Ks isoforms (PI3K-C2α, PI3K-C2β, and PI3K-C2γ) have distinct and non-overlapping cellular roles. Here, ...
Source: Trends in Cell Biology - January 25, 2019 Category: Cytology Authors: Gulluni F, De Santis MC, Margaria JP, Martini M, Hirsch E Tags: Trends Cell Biol Source Type: research

Functions of Microtubule Disassembly during Neurite Pruning.
Abstract Large-scale neurite pruning, the developmentally regulated degeneration of axons or dendrites, is an important specificity mechanism during neuronal circuit formation. Pruning is usually restricted to single neurite branches and can occur by local degeneration or retraction. How this spatial regulation is achieved, and what triggers degeneration locally, are still poorly understood. At the cellular level, pruning involves local cytoskeleton disassembly before branch removal. Recent evidence suggests that microtubule disassembly is the local trigger and that the specific local microtubule organization of a...
Source: Trends in Cell Biology - January 22, 2019 Category: Cytology Authors: Rumpf S, Wolterhoff N, Herzmann S Tags: Trends Cell Biol Source Type: research

Intersections between Regulated Cell Death and Autophagy.
Abstract In multicellular organisms, cell death is an essential aspect of life. Over the past decade, the spectrum of different forms of regulated cell death (RCD) has expanded dramatically with relevance in several pathologies such as inflammatory and neurodegenerative diseases. This has been paralleled by the growing awareness of the central importance of autophagy as a stress response that influences decisions of cell life and cell death. Here, we first introduce criteria and methodologies for correct identification of the different RCD forms. We then discuss how the autophagy machinery is directly associated w...
Source: Trends in Cell Biology - January 18, 2019 Category: Cytology Authors: Napoletano F, Baron O, Vandenabeele P, Mollereau B, Fanto M Tags: Trends Cell Biol Source Type: research

Targeting Cancer through the Epigenetic Features of Telomeric Regions.
cute; Abstract The integrity of the chromatin associated with telomeric regions, which include telomeres and subtelomeres, is essential for telomeres function and cell viability. Whereas human subtelomeres are heterochromatic, telomeres are labeled with euchromatic marks like H4K20me1 and H3K27ac in most commonly studied human cell lines. The epigenetic marks of human telomeric regions influence oncogenic processes. Indeed, different drugs that decrease their genome-wide levels are currently being used or tested in specific cancer therapies. These drugs can challenge cancer by altering the function of key cellular...
Source: Trends in Cell Biology - January 16, 2019 Category: Cytology Authors: Vaquero-Sedas MI, Vega-Palas MÁ Tags: Trends Cell Biol Source Type: research

Therapeutic Dissolution of Aberrant Phases by Nuclear-Import Receptors.
Abstract Nuclear-import receptors (NIRs) bind nuclear-localization signals (NLSs) of protein cargo in the cytoplasm and transport them into the nucleus. Here, we review advances establishing that NIRs also function in the cytoplasm to prevent and reverse functional and aberrant phase transitions of their cargo, including neurodegenerative disease-linked RNA-binding proteins (RBPs) with prion-like domains, such as TDP-43, FUS, hnRNPA1, and hnRNPA2. NIRs selectively extract cargo from condensed liquid phases thereby regulating functional phase separation. Consequently, NIRs sculpt cytoplasmic membraneless organelles...
Source: Trends in Cell Biology - January 16, 2019 Category: Cytology Authors: Guo L, Fare CM, Shorter J Tags: Trends Cell Biol Source Type: research

Ion Channel Conformations Regulate Integrin-Dependent Signaling.
Abstract Cell-matrix adhesion determines the choice between different cell fates and is accompanied by substantial changes in ion transport. The greatest evidence is the bidirectional interplay occurring between integrin receptors and K+ channels. These proteins can form signaling hubs that regulate cell proliferation, differentiation, and migration in normal and neoplastic tissue. Recent results show that the physical interaction with integrins determines the balance of the open and closed K+ channel states, and individual channel conformations regulate distinct downstream pathways. We propose a model of how thes...
Source: Trends in Cell Biology - January 8, 2019 Category: Cytology Authors: Becchetti A, Petroni G, Arcangeli A Tags: Trends Cell Biol Source Type: research

RNA: Nuclear Glue for Folding the Genome.
Abstract A significant amount of RNA is present in the nucleus of mammalian cells but only a small proportion of it is destined for the cytoplasm and subsequent translation, leaving much RNA to associate with chromatin. Historically, nuclear RNA was thought to interact with proteins to form a filamentous nuclear matrix, but this idea became less popular as more dynamic models of chromatin behaviour became more prevalent. Using new molecular and imaging approaches it is becoming clear that RNA should be considered an integral component of nuclear organisation; it is transcriptionally responsive and interacts with a...
Source: Trends in Cell Biology - January 7, 2019 Category: Cytology Authors: Nozawa RS, Gilbert N Tags: Trends Cell Biol Source Type: research

From Flat to Curved Clathrin: Controlling a Plastic Ratchet.
Abstract Clathrin-mediated endocytosis (CME) is the primary mechanism eukaryotic cells use to internalize material. New imaging tools are revealing the nanoscale structural dynamics of single clathrin-coated sites. Recently, it has become clear that the structure and dynamics of clathrin - flat clathrin lattices and the transition to highly curved clathrin-coated vesicles - are adaptable and can follow many paths. Thus, understanding this dynamic plasticity will lead to insights into how one molecular machine can participate in multiple pathways and adapt to changing and diverse cellular environments. Here, we rev...
Source: Trends in Cell Biology - December 28, 2018 Category: Cytology Authors: Sochacki KA, Taraska JW Tags: Trends Cell Biol Source Type: research

EMT Transition States during Tumor Progression and Metastasis.
Abstract Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states. Here, we review the recent studies that demonstrate the existence of these different EMT states in cancer and the mechanisms regulating their functions. We discuss the different functional characteristics, such as proliferation, propagation, plasticity, invasion, and metastasis associate...
Source: Trends in Cell Biology - December 26, 2018 Category: Cytology Authors: Pastushenko I, Blanpain C Tags: Trends Cell Biol Source Type: research

Nucleus-Invadopodia Duo During Cancer Invasion.
Abstract Matrix proteolysis mediated by MT1-MMP facilitates the invasive migration of tumor cells in dense tissues, which otherwise get trapped in the matrix because of limited nuclear deformability. A digest-on-demand response has been identified, which requires nucleus-microtubule linkage through the LINC complex and triggers MT1-MMP surface-exposure to facilitate nucleus movement. PMID: 30573318 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - December 17, 2018 Category: Cytology Authors: Ferrari R, Infante E, Chavrier P Tags: Trends Cell Biol Source Type: research

The Battle between TET Proteins and DNA Methylation for the Right Cell: (Trends in Cell Biology 28, 973-975, 2018).
PMID: 30545791 [PubMed - as supplied by publisher] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - December 10, 2018 Category: Cytology Authors: Li D, Chen J, Pei D Tags: Trends Cell Biol Source Type: research

Structural Insights into the Mechanism of Dynamin Superfamily Proteins.
Abstract Dynamin superfamily proteins (DSPs) mediate membrane fission and fusion necessary for endocytosis, organelle biogenesis and maintenance, as well as for bacterial cytokinesis. They also function in the innate immune response to pathogens and in organizing the cytoskeleton. In this review, we summarize the current understanding of the molecular mechanism of DSPs, with emphasis on the structural basis of function. Studies from the past decade on the structure and mechanism of DSPs enable comparative analysis of shared mechanisms and unique features of this protein family. PMID: 30527453 [PubMed - as sup...
Source: Trends in Cell Biology - December 5, 2018 Category: Cytology Authors: Jimah JR, Hinshaw JE Tags: Trends Cell Biol Source Type: research

Novel Roles for SUMOylation in Cellular Plasticity.
Abstract Cell fate transitions involve rapid changes in gene expression patterns, yet the role of post-translational modifications in these processes remains underexplored. A recent study identifies SUMOylation as a guardian of cell identity that acts during differentiation and reprogramming by reinforcing active enhancers and maintaining silenced heterochromatin in a context-specific manner. PMID: 30463679 [PubMed - in process] (Source: Trends in Cell Biology)
Source: Trends in Cell Biology - November 23, 2018 Category: Cytology Authors: Di Stefano B, Hochedlinger K Tags: Trends Cell Biol Source Type: research