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Trends in Cell Biology

Anup Parchure, Neha Vyas, Satyajit Mayor
Morphogens are signaling molecules produced by a localized source, specifying cell fate in a graded manner. The source secretes morphogens into the extracellular milieu to activate various target genes in an autocrine or paracrine manner. Here we describe various secreted forms of two canonical morphogens, the lipid-anchored Hedgehog (Hh) and Wnts, indicating the involvement of multiple carriers in the transport of these morphogens. These different extracellular secreted forms are likely to have distinct functions...
November 10, 2017: Trends in Cell Biology
Deepak P Patil, Brian F Pickering, Samie R Jaffrey
N(6)-Methyladenosine (m(6)A) is the most prevalent post-transcriptional modification of eukaryotic mRNA and long noncoding RNA. m(6)A mediates its effects primarily by recruiting proteins, including the multiprotein eukaryotic initiation factor 3 complex and a set of proteins that contain the YTH domain. Here we describe the mechanisms by which YTH domain-containing proteins bind m(6)A and influence the fate of m(6)A-containing RNA in mammalian cells. We discuss the diverse, and occasionally contradictory, functions ascribed to these proteins and the emerging concepts that are influencing our understanding of these proteins and their effects on the epitranscriptome...
November 2, 2017: Trends in Cell Biology
Fukun Guo, Yi Zheng
A recent study shows that the protumorigenic guanine nucleotide exchange factor (GEF) Vav1 functions as a tumor suppressor in T cell acute lymphoblastic leukemia (T-ALL) through its ability to complex with the Cbl-b ubiquitin ligase and the intracellular domain of Notch1 (ICN1) and to promote ICN1 degradation. Vav1can act as a double-edged sword in tumorigenesis.
October 30, 2017: Trends in Cell Biology
Lendert Gelens, Junbin Qian, Mathieu Bollen, Adrian T Saurin
Kinases and phosphatases work antagonistically to control the behaviour of individual substrate molecules. This can be incorrectly extrapolated to imply that they also work antagonistically on the signals or processes that these molecules control. In fact, in many situations kinases and phosphatases work together to positively drive signal responses. We explain how this 'cooperativity' is critical for setting the amplitude, localisation, timing, and shape of phosphorylation signals. We use mitosis to illustrate why these properties are important for controlling mitotic entry, sister chromatid cohesion, kinetochore-microtubule attachments, the spindle assembly checkpoint, mitotic spindle elongation, and mitotic exit...
October 28, 2017: Trends in Cell Biology
Curtis R Warren, Chad A Cowan
Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype. Recent publications have described iPSC cohort studies of common genetic variants and their effects on gene expression and cellular phenotypes. These in vitro quantitative trait locus (QTL) studies are the first experiments in a new paradigm with great potential: iPSC-based functional population genetic studies. iPSC collections from large cohorts are currently under development to facilitate the next wave of these studies, which have the potential to discover the effects of common genetic variants on cellular phenotypes and to uncover the molecular basis of common genetic diseases...
October 17, 2017: Trends in Cell Biology
Lee Dolat, Raphael H Valdivia
Intracellular bacterial pathogens thrive within eukaryotic cells by interacting with a range of organelles to establish a replicative niche. In a new study in Cell Host and Microbe, Miller et al. identify a Brucella abortus effector that subverts membrane and protein transport to the Golgi apparatus to promote bacterial replication.
October 4, 2017: Trends in Cell Biology
Stephen M Hinshaw, Stephen C Harrison
During a single human lifetime, nearly one quintillion chromosomes separate from their sisters and transit to their destinations in daughter cells. Unlike DNA replication, chromosome segregation has no template, and, unlike transcription, errors frequently lead to a total loss of cell viability. Rapid progress in recent years has shown how kinetochores enable faithful execution of this process by connecting chromosomal DNA to microtubules. These findings have transformed our idea of kinetochores from cytological features to immense molecular machines and now allow molecular interpretation of many long-appreciated kinetochore functions...
October 3, 2017: Trends in Cell Biology
Andrei Smertenko, Farhah Assaad, František Baluška, Magdalena Bezanilla, Henrik Buschmann, Georgia Drakakaki, Marie-Theres Hauser, Marcel Janson, Yoshinobu Mineyuki, Ian Moore, Sabine Müller, Takashi Murata, Marisa S Otegui, Emmanuel Panteris, Carolyn Rasmussen, Anne-Catherine Schmit, Jozef Šamaj, Lacey Samuels, L Andrew Staehelin, Daniel Van Damme, Geoffrey Wasteneys, Viktor Žárský
Plant cytokinesis is orchestrated by a specialized structure, the phragmoplast. The phragmoplast first occurred in representatives of Charophyte algae and then became the main division apparatus in land plants. Major cellular activities, including cytoskeletal dynamics, vesicle trafficking, membrane assembly, and cell wall biosynthesis, cooperate in the phragmoplast under the guidance of a complex signaling network. Furthermore, the phragmoplast combines plant-specific features with the conserved cytokinetic processes of animals, fungi, and protists...
September 21, 2017: Trends in Cell Biology
Alejandro López-Soto, Segundo Gonzalez, Carlos López-Larrea, Guido Kroemer
A wide array of cell-intrinsic surveillance mechanisms maintains the homeostasis of dividing cells and the integrity of the genome. Accumulating evidence also supports a role for cell-extrinsic mechanisms. Among them, the immune system, together with cell-autonomous checkpoint processes, eliminates cells that harbor unbalanced karyotypes generated by mitotic defects.
September 19, 2017: Trends in Cell Biology
Shoichiro Kameoka, Yoshihiro Adachi, Koji Okamoto, Miho Iijima, Hiromi Sesaki
Membrane organelles comprise both proteins and lipids. Remodeling of these membrane structures is controlled by interactions between specific proteins and lipids. Mitochondrial structure and function depend on regulated fusion and the division of both the outer and inner membranes. Here we discuss recent advances in the regulation of mitochondrial dynamics by two critical phospholipids, phosphatidic acid (PA) and cardiolipin (CL). These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases...
September 11, 2017: Trends in Cell Biology
Peter Ly, Don W Cleveland
Cancer genome sequencing has identified chromothripsis, a complex class of structural genomic rearrangements involving the apparent shattering of an individual chromosome into tens to hundreds of fragments. An initial error during mitosis, producing either chromosome mis-segregation into a micronucleus or chromatin bridge interconnecting two daughter cells, can trigger the catastrophic pulverization of the spatially isolated chromosome. The resultant chromosomal fragments are religated in random order by DNA double-strand break repair during the subsequent interphase...
September 9, 2017: Trends in Cell Biology
Rebecca de Leeuw, Yosef Gruenbaum, Ohad Medalia
The nuclear lamina is a nuclear peripheral meshwork that is mainly composed of nuclear lamins, although a small fraction of lamins also localizes throughout the nucleoplasm. Lamins are classified as type V intermediate filament (IF) proteins. Mutations in lamin genes cause at least 15 distinct human diseases, collectively termed laminopathies, including muscle, metabolic, and neuronal diseases, and can cause accelerated aging. Most of these mutations are in the LMNA gene encoding A-type lamins. A growing number of nuclear proteins are known to bind lamins and are implicated in both nuclear and cytoskeletal organization, mechanical stability, chromatin organization, signaling, gene regulation, genome stability, and cell differentiation...
September 8, 2017: Trends in Cell Biology
Jian Li, Johnathan Labbadia, Richard I Morimoto
The heat shock response (HSR) was originally discovered as a transcriptional response to elevated temperature shock and led to the identification of heat shock proteins and heat shock factor 1 (HSF1). Since then HSF1 has been shown to be important for combating other forms of environmental perturbations as well as genetic variations that cause proteotoxic stress. The HSR has long been thought to be an absolute response to conditions of cell stress and the primary mechanism by which HSF1 promotes organismal health by preventing protein aggregation and subsequent proteome imbalance...
September 7, 2017: Trends in Cell Biology
Raquel Espin-Palazon, Bart Weijts, Victor Mulero, David Traver
Hematopoietic stem cells (HSCs) have the extraordinary ability to both self-renew and generate all mature blood cell lineages. The ability to produce or expand patient-derived HSCs in vitro would greatly improve the outcome for patients with blood disorders that are currently treated with allogeneic HSC transplantation. Many laboratories have been working to identify the signals required for HSC emergence in their native environments to apply this knowledge in vitro. Recently, several signals traditionally known to underlie classical inflammation have emerged as essential regulators of HSC development...
September 4, 2017: Trends in Cell Biology
Daniel G Booth, William C Earnshaw
The chromosome periphery is a complex network of proteins and RNA molecules (many derived from nucleoli) that covers the outer surface of chromosomes and whose function remains mysterious. Although it was first described over 130 years ago, technological advances and the recent discovery that Ki-67 acts as an organiser of this region have allowed the chromosome periphery to be dissected in previously unattainable detail, leading to a revival of interest in this obscure chromosomal compartment. Here, we review the most recent advances into the composition, structure and function of the chromosome periphery, discuss possible roles of Ki-67 during mitosis and consider why this structure is likely to remain the focus of ongoing attention in the future...
August 21, 2017: Trends in Cell Biology
Matyas Abel Tsegaye, Zachary T Schafer
A hallmark of pancreatic ductal adenocarcinoma cancer (PDAC) cells is metabolic reprogramming that facilitates tumor progression. In a recent paper published in Molecular Cell, Nagarajan et al. discover that paraoxonase (PON)2 stimulates glucose transporter (GLUT)1-mediated glucose uptake, prevents AMP-activated protein kinase (AMPK)-mediated anoikis, and consequently promotes PDAC development and metastasis.
November 2017: Trends in Cell Biology
Amy E Vincent, Doug M Turnbull, Veronica Eisner, György Hajnóczky, Martin Picard
Insight into the regulation of complex physiological systems emerges from understanding how biological units communicate with each other. Recent findings show that mitochondria communicate at a distance with each other via nanotunnels, thin double-membrane protrusions that connect the matrices of non-adjacent mitochondria. Emerging evidence suggest that mitochondrial nanotunnels are generated by immobilized mitochondria and transport proteins. This review integrates data from the evolutionarily conserved structure and function of intercellular projections in bacteria with recent developments in mitochondrial imaging that permit nanotunnel visualization in eukaryotes...
November 2017: Trends in Cell Biology
Ashley M Thelen, Roberto Zoncu
Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase...
November 2017: Trends in Cell Biology
Yoko Ito, Matthew Hoare, Masashi Narita
Cellular senescence is an autonomous tumor suppressor mechanism leading to stable cell cycle arrest. Senescent cells are highly secretory, driving a range of different functions through the senescence-associated secretory phenotype (SASP). Recent findings have suggested that the composition of the SASP is dynamically and spatially regulated and that the changing composition of the SASP can determine the beneficial and detrimental aspects of the senescence program, tipping the balance to either an immunosuppressive/profibrotic environment or proinflammatory/fibrolytic state...
November 2017: Trends in Cell Biology
Costas A Lyssiotis, Alec C Kimmelman
Tumors are dynamic pseudoorgans that contain numerous cell types interacting to create a unique physiology. Within this network, the malignant cells encounter many challenges and rewire their metabolic properties accordingly. Such changes can be experienced and executed autonomously or through interaction with other cells in the tumor. The focus of this review is on the remodeling of the tumor microenvironment that leads to pathophysiologic interactions that are influenced and shaped by metabolism. They include symbiotic nutrient sharing, nutrient competition, and the role of metabolites as signaling molecules...
November 2017: Trends in Cell Biology
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