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Trends in Cell Biology

Christophe Viret, Mathias Faure
During macroautophagy, cytosolic elements are confined in autophagosomes before fusion with endolysosomes for degradation or recycling. Recruitment of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) factor syntaxin 17 (STX17) is instrumental for this maturation step. Two recent studies indicate that the kinase ULK1 and the apoptosis modulator BRUCE both regulate STX17 engagement during autophagosome maturation in mammalian cells.
November 8, 2018: Trends in Cell Biology
Dongwei Li, Jiekai Chen, Duanqing Pei
DNA methylation is an important epigenetic barrier during somatic cell reprogramming. Yet, how genome-wide methylation is reprogrammed remains largely unknown. Sardina et al. [6] (Cell Stem Cell 2018: address this question by mapping the DNA methylomes of cells undergoing reprogramming and show that TET proteins and transcription factors cooperate to orchestrate demethylation critical to reprogramming.
November 3, 2018: Trends in Cell Biology
Priti Agarwal, Ronen Zaidel-Bar
The actomyosin cytoskeleton is responsible for most force-driven processes in cells and tissues. How it assembles into the necessary structures at the right time and place is an important question. Here, we focus on molecular mechanisms of actomyosin regulation recently elucidated in animal models, and highlight several common principles that emerge. The architecture of the actomyosin network - an important determinant of its function - results from actin polymerization, crosslinking and turnover, localized myosin activation, and contractility-driven self-organization...
October 29, 2018: Trends in Cell Biology
Tânia Perestrelo, Marcelo Correia, João Ramalho-Santos, Denis Wirtz
The ability to shift between metabolic states and to tightly regulate cellular mechanical properties have been described as crucial events in the achievement of correct embryonic development. Indeed, metabolic and mechanical manipulations in vitro have led to the discovery of new methods to control cell fate. As these two modulators are usually studied separately, in this review article, we describe how cellular mechanics and metabolic characteristics regulate embryonic development in vivo and describe the role of these cues in the regulation of pluripotency and differentiation in vitro...
October 22, 2018: Trends in Cell Biology
Katharina Papsdorf, Anne Brunet
The lifespan of an organism is strongly influenced by environmental factors (including diet) and by internal factors (notably reproductive status). Lipid metabolism is critical for adaptation to external conditions or reproduction. Interestingly, specific lipid profiles are associated with longevity, and increased uptake of certain lipids extends longevity in Caenorhabditis elegans and ameliorates disease phenotypes in humans. How lipids impact longevity, and how lipid metabolism is regulated during aging, is just beginning to be unraveled...
October 10, 2018: Trends in Cell Biology
Zi Ye, Casim A Sarkar
Cells have traditionally been characterized using expression levels of a few proteins that are thought to specify phenotype. This requires a priori selection of proteins, which can introduce descriptor bias, and neglects the wealth of additional molecular information nested within each cell in a population, which often makes these sparse descriptors qualitative. Recently, more unbiased and quantitative cell characterization has been made possible by new high-throughput, information-dense experimental approaches and data-driven computational methods...
October 8, 2018: Trends in Cell Biology
Michael Piper, Richard Gronostajski, Graziella Messina
The past decade has seen incredible advances in the field of stem cell biology that have greatly improved our understanding of development and provided important insights into pathological processes. Transcription factors (TFs) play a central role in mediating stem cell proliferation, quiescence, and differentiation. One TF that contributes to these processes is Nuclear Factor One X (NFIX). Recently, NFIX activity has been shown to be essential in multiple organ systems and to have important translational impacts for human health...
October 1, 2018: Trends in Cell Biology
Maja Milanovic, Yong Yu, Clemens A Schmitt
Activated oncogenes or anticancer therapies evoke senescent cell-cycle arrest in (pre-)malignant cells, thereby interrupting tumor formation or progression. Physiologically, cellular senescence contributes to embryonic development and tissue regeneration. These observations and the overlap of numerous gene products in senescence and stem cell signaling prompted investigations into whether epigenetic establishment of the senescent state may concomitantly reprogram the cell into a latent stem-like condition, whose functional impact becomes evident when arrested cells resume proliferation...
September 22, 2018: Trends in Cell Biology
Barbara Grünwald, Benjamin Schoeps, Achim Krüger
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a major player in preserving tissue integrity and has recently also emerged as a decisive factor in several human pathologies. This appreciation has prompted this review addressing the largely underestimated complexity of the functions executed by TIMP-1 and their mechanistic basis. In fact, the versatile impact of TIMP-1 on cellular functions stems from its two-domain structure harboring metalloproteinase-inhibitory and cytokine-like signaling activities...
September 19, 2018: Trends in Cell Biology
Barbara J Mann, Patricia Wadsworth
Chromosome segregation during cell division requires a bipolar mitotic spindle. Therefore, how the spindle is formed, maintained, and functions is of fundamental importance for all eukaryotic cells. Members of the evolutionarily conserved kinesin-5 family of motor proteins have been shown to play an essential role in spindle formation by generating forces that establish and maintain spindle bipolarity and contribute to spindle elongation. Recent work demonstrates that accessory proteins and post-translational modifications regulate the localization and activity of kinesin-5 motors in cells...
September 13, 2018: Trends in Cell Biology
Lorenzo Galluzzi, Stefani Spranger, Elaine Fuchs, Alejandro López-Soto
Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy...
September 13, 2018: Trends in Cell Biology
Joppe Nieuwenhuis, Thijn R Brummelkamp
Microtubules are subjected to a variety of post-translational modifications (PTMs). The combination of different α- and β-tubulin isoforms and PTMs are referred to as the tubulin code. PTMs are generated by a suite of enzymes thought to affect tubulin-interacting proteins. One PTM is the cyclic removal and ligation of the C-terminal tyrosine of α-tubulin. This has been implicated in cellular processes such as mitosis, cardiomyocyte contraction, and neuronal function. Recently, vasohibins (VASHs) were identified as the first tubulin-detyrosinating enzymes, A cell-autonomous role for VASHs in regulating the cytoskeleton was unexpected due to their previous association with angiogenesis...
September 10, 2018: Trends in Cell Biology
António J M Santos, Yuan-Hung Lo, Amanda T Mah, Calvin J Kuo
The intestinal epithelium is a rapidly renewing cellular compartment. This constant regeneration is a hallmark of intestinal homeostasis and requires a tightly regulated balance between intestinal stem cell (ISC) proliferation and differentiation. Since intestinal epithelial cells directly contact pathogenic environmental factors that continuously challenge their integrity, ISCs must also actively divide to facilitate regeneration and repair. Understanding niche adaptations that maintain ISC activity during homeostatic renewal and injury-induced intestinal regeneration is therefore a major and ongoing focus for stem cell biology...
September 5, 2018: Trends in Cell Biology
Urjita Joshi, Joseline A Houwman, Peter van der Sluijs
Lysosome function and position in the cytoplasm depends on the BORCS machinery, which tethers lysosomes to the kinesin microtubule motor. A recent paper of Snouwaert et al. in Cell Reports characterizes a mouse with a spontaneous mutation in the Borcs7 subunit, which causes axonal dystrophy and impaired motor function.
September 2, 2018: Trends in Cell Biology
Helen Loo Yau, Ilias Ettayebi, Daniel D De Carvalho
During cancer initiation and progression, the somatic epigenome is broadly reprogrammed. This reprogramming can be a consequence of several processes, including altered transcriptional profiles and mutations. In addition, immune cells infiltrating the tumor microenvironment display a reprogrammed epigenome. For instance, tumor infiltrating T cells frequently exhibit an exhausted phenotype characterized by aberrant DNA methylation. Moreover, these aberrant epigenomes of cancer cells and infiltrating immune cells may represent a cancer vulnerability...
August 25, 2018: Trends in Cell Biology
Abigail K Corona, William T Jackson
Autophagosome/amphisome-lysosome fusion is a highly regulated process at the protein, lipid, and biochemical level. Each primary component of fusion, such as the core SNAREs, HOPS complex, or physical positioning by microtubule-associated dynein motors, are regulated at multiple points to ensure optimum conditions for autophagic flux to proceed. With the complexity of the membrane fusion system, it is not difficult to imagine how autophagic flux defect-related disorders, such as Huntington's disease, non-familial Alzheimer's disease, and Vici syndrome develop...
November 2018: Trends in Cell Biology
Elodie Villa, Sandrine Marchetti, Jean-Ehrland Ricci
Mitochondria are essential highly dynamic organelles that provide the necessary energy for a variety of different processes, such as survival, proliferation, and migration. In order to maintain an intact mitochondrial network, cells have developed quality control systems that allow the removal of damaged or superfluous mitochondria by selective mitochondrial autophagy called mitophagy. Although the parkin/PINK1 axis is often considered the main regulator of mitophagy, a growing body of evidence has shown that this pathway is not unique and that mitophagy can still be functional in the absence of parkin...
November 2018: Trends in Cell Biology
Mary Williard Elting, Pooja Suresh, Sophie Dumont
The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle...
November 2018: Trends in Cell Biology
Ana Rita Nobre, David Entenberg, Yarong Wang, John Condeelis, Julio A Aguirre-Ghiso
Hypoxia is linked to metastasis; however, how it affects metastatic progression is not clear due to limited consensus in the literature. We posit that this lack of consensus is due to hypoxia being studied using different approaches, such as in vitro, primary tumor, or metastasis assays in an isolated manner. Here, we review the pros and cons of in vitro hypoxia assays, highlight in vivo studies that inform on physiological hypoxia, and review the evidence that primary tumor hypoxia might influence the fate of disseminated tumor cells (DTCs) in secondary organs...
November 2018: Trends in Cell Biology
Lars Langemeyer, Florian Fröhlich, Christian Ungermann
Eukaryotic cells maintain a highly organized endolysosomal system. This system regulates the protein and lipid content of the plasma membrane, it participates in the intracellular quality control machinery and is needed for the efficient removal of damaged organelles. This complex network comprises an endosomal membrane system that feeds into the lysosomes, yet also allows recycling of membrane proteins, and probably lipids. Moreover, lysosomal degradation provides the cell with macromolecules for further growth...
November 2018: Trends in Cell Biology
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