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Trends in Cell Biology

Patrick T Caswell, Tobias Zech
Cell migration controls developmental processes (gastrulation and tissue patterning), tissue homeostasis (wound repair and inflammatory responses), and the pathobiology of diseases (cancer metastasis and inflammation). Understanding how cells move in physiologically relevant environments is of major importance, and the molecular machinery behind cell movement has been well studied on 2D substrates, beginning over half a century ago. Studies over the past decade have begun to reveal the mechanisms that control cell motility within 3D microenvironments - some similar to, and some highly divergent from those found in 2D...
June 30, 2018: Trends in Cell Biology
Haaris Ahsan Safdari, Shubhi Pandey, Arun K Shukla, Somnath Dutta
The wave of resolution revolution in cryo-EM has touched, and made a significant impact on, the structural biology of GPCRs. High-resolution structures of several GPCR-G-protein complexes are now determined by cryo-EM and they illuminate fine structural details of this central macromolecular complex involved in cellular signaling.
June 23, 2018: Trends in Cell Biology
Yaron Shav-Tal, Timir Tripathi
Nucleoporin subunits that generate the nuclear pore complex (NPC) are highly conserved in evolution. High-resolution structures of the NPC are available, but the actual NPC composition in yeast has only been quantified recently. Two studies reveal major differences between species, suggesting high flexibility in NPC structures during evolution.
June 22, 2018: Trends in Cell Biology
Yifan Zhang, Shuai Gao, Jun Xia, Feng Liu
The classical roadmap of hematopoietic hierarchy has been proposed for nearly 20 years and has become a dogma of stem cell research for most types of adult stem cells, including hematopoietic stem cells (HSCs). However, with the development of new technologies such as omics approaches at single-cell resolution, recent studies in vitro and in vivo have suggested that heterogeneity is a common feature of HSCs and their progenies. While these findings broaden our understanding of hematopoiesis, they also challenge the well-accepted hematopoietic hierarchy roadmap...
June 20, 2018: Trends in Cell Biology
Andrea J Schorn, Rob Martienssen
tRNA fragments (tRFs) are a class of small, regulatory RNAs with diverse functions. 3'-Derived tRFs perfectly match long terminal repeat (LTR)-retroelements which use the 3'-end of tRNAs to prime reverse transcription. Recent work has shown that tRFs target LTR-retroviruses and -transposons for the RNA interference (RNAi) pathway and also inhibit mobility by blocking reverse transcription. The highly conserved tRNA primer binding site (PBS) in LTR-retroelements is a unique target for 3'-tRFs to recognize and block abundant but diverse LTR-retrotransposons that become transcriptionally active during epigenetic reprogramming in development and disease...
June 19, 2018: Trends in Cell Biology
Anna Sahakyan, Yihao Yang, Kathrin Plath
In each somatic cell of a female mammal one X chromosome is transcriptionally silenced via X-chromosome inactivation (XCI), initiating early in development. Although XCI events are conserved in mouse and human postimplantation development, regulation of X-chromosome dosage in preimplantation development occurs differently. In preimplantation development, mouse embryos undergo imprinted form of XCI, yet humans lack imprinted XCI and instead regulate gene expression of both X chromosomes by dampening transcription...
June 14, 2018: Trends in Cell Biology
Veronica Ortiz, Min Yu
Whole-genome sequencing has made a significant impact on cancer research, but traditional bulk methods fail to detect information from rare cells. Recently developed single-cell sequencing methods have provided new insights and unprecedented details about cancer progression and diversity. These advancements also enable the investigation of rare cells, such as circulating tumor cells (CTCs) derived from cancer patients. In this review, we outline various single-cell sequencing techniques that can elucidate the molecular properties of CTCs...
June 8, 2018: Trends in Cell Biology
Michel O Steinmetz, Andrea E Prota
Microtubule-targeting agents (MTAs) such as paclitaxel and the vinca alkaloids are among the most important medical weapons available to combat cancer. MTAs interfere with intracellular transport, inhibit eukaryotic cell proliferation, and promote cell death by suppressing microtubule dynamics. Recent advances in the structural analysis of MTAs have enabled the extensive characterization of their interactions with microtubules and their building block tubulin. We review here our current knowledge on the molecular mechanisms used by MTAs to hijack the microtubule cytoskeleton, and discuss dual inhibitors that target both kinases and microtubules...
June 2, 2018: Trends in Cell Biology
Edward E Morrisey, Anil K Rustgi
Lung and esophageal development and organogenesis involve a complex interplay of signaling pathways and transcriptional factors. Once the lung and esophagus do separate, their epithelial proliferation and differentiation programs share certain common properties that may fuel adaptive responses to injury and subsequent regeneration. Lung and esophageal tissue organogenesis and regeneration provide perspectives on squamous cell cancers and adenocarcinomas in each tissue.
June 2, 2018: Trends in Cell Biology
Sobhika Agarwala, Owen J Tamplin
The hematopoietic stem cell (HSC) niche supports steady-state hematopoiesis and responds to changing needs during stress and disease. The nervous system is an important regulator of the niche, and its influence is established early in development when stem cells are specified. Most research has focused on direct innervation of the niche, however recent findings show there are different modes of neural control, including globally by the central nervous system (CNS) and hormone release, locally by neural crest-derived mesenchymal stem cells, and intrinsically by hematopoietic cells that express neural receptors and neurotransmitters...
May 29, 2018: Trends in Cell Biology
Emanuel Rognoni, Fiona M Watt
Skin architecture and function depend on diverse populations of epidermal cells and dermal fibroblasts. Reciprocal communication between the epidermis and dermis plays a key role in skin development, homeostasis and repair. While several stem cell populations have been identified in the epidermis with distinct locations and functions, it is now recognised that there is additional heterogeneity within the mesenchymal cells of the dermis. Here, we discuss recent insights into how these distinct cell populations are maintained and coordinated during development, homeostasis, and wound healing...
May 25, 2018: Trends in Cell Biology
Bruce L Goode, Meredith O Sweeney, Julian A Eskin
Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex...
May 18, 2018: Trends in Cell Biology
Cynthia J Sieben, Ines Sturmlechner, Bart van de Sluis, Jan M van Deursen
Damaged cells at risk of neoplastic transformation can be neutralized by apoptosis or engagement of the senescence program, which induces permanent cell-cycle arrest and a bioactive secretome that is implicated in tumor immunosurveillance. While from an evolutionary perspective senescence is beneficial in that it protects against malignancies, the accumulation of senescent cells in tissues and organs with aging and at sites of various pathologies is largely detrimental. Because induction of senescence in cancer cells is emerging as a therapeutic concept, it will be important to consider these detrimental effects, including tumor-promoting properties that may drive the formation of secondary tumors or cancer relapse...
May 15, 2018: Trends in Cell Biology
Ryan Rickels, Ali Shilatifard
Enhancers are distally located genomic cis-regulatory elements that integrate spatiotemporal cues to coordinate gene expression in a tissue-specific manner during metazoan development. Enhancer function depends on a combination of bound transcription factors and cofactors that regulate local chromatin structure, as well as on the topological interactions that are necessary for their activity. Numerous genome-wide studies concur that the vast majority of disease-associated variations occur within non-coding genomic sequences, in other words the 'cis-regulome', and this underscores their relevance for human health...
May 11, 2018: Trends in Cell Biology
Pin Li, Adekunle T Bademosi, Jincai Luo, Frederic A Meunier
Cellular communication relies on fusion of secretory vesicles with the plasma membrane, following dynamic events that change the micro- and nanoscale environment of the approaching vesicles in the vicinity of docking sites. Visualization of fine cortical actin network structures and their interactions with vesicle and plasma membrane has recently been facilitated by the development of new imaging technologies. Consequently, a greater understanding is emerging of the role of the cortical actin network on controlling secretory vesicles as they undergo docking, priming, and fusion in exocytic hot spots...
May 11, 2018: Trends in Cell Biology
Ilaria Elia, Ginevra Doglioni, Sarah-Maria Fendt
Metastasis to distant organs is a predictor of poor prognosis. Therefore, it is of paramount importance to understand the mechanisms that impinge on the different steps of the metastatic cascade. Recent work has revealed that particular metabolic pathways are rewired in cancer cells to support their transition through the metastatic cascade, resulting in the formation of secondary tumors in distant organs. Indeed, metabolic rewiring induces signaling pathways during initial cancer invasion, circulating cancer cells depend on enhanced antioxidant defenses, and cancer cells colonizing a distant organ require increased ATP production...
May 7, 2018: Trends in Cell Biology
Vassiliki Nikoletopoulou, Nektarios Tavernarakis
Genetic studies have demonstrated that conditional ablation of core autophagy genes in the neural lineage leads to progressive neurodegeneration, indicating that this catabolic pathway is indispensable for neuronal maintenance. However, accumulating evidence also indicates that autophagy is not merely a housekeeping process. Instead, autophagy may be dynamically regulated in different neuronal compartments and dictate the turnover of selected cargo in a time- and space-dependent manner and thus contribute to specialized neuronal functions...
May 3, 2018: Trends in Cell Biology
Luisa Cimmino, Benjamin G Neel, Iannis Aifantis
Vitamin C is an essential dietary requirement for humans. In addition to its known role as an antioxidant, vitamin C is a cofactor for Fe2+ - and α-ketoglutarate-dependent dioxygenases (Fe2+ /α-KGDDs) which comprise a large number of diverse enzymes, including collagen prolyl hydroxylases and epigenetic regulators of histone and DNA methylation. Vitamin C can modulate embryonic stem cell (ESC) function, enhance reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs), and hinder the aberrant self-renewal of hematopoietic stem cells (HSCs) through its ability to enhance the activity of either Jumonji C (JmjC) domain-containing histone demethylases or ten-eleven translocation (TET) DNA hydroxylases...
April 30, 2018: Trends in Cell Biology
Varnesh Tiku, Adam Antebi
The nucleolus is a prominent membraneless organelle residing within the nucleus. The nucleolus has been regarded as a housekeeping structure mainly known for its role in ribosomal RNA (rRNA) production and ribosome assembly. However, accumulating evidence has revealed its functions in numerous cellular processes that control organismal physiology, thereby taking the nucleolus much beyond its conventional role in ribosome biogenesis. Perturbations in nucleolar functions have been associated with severe diseases such as cancer and progeria...
April 27, 2018: Trends in Cell Biology
Axel T Brunger, Jeremy Leitz, Qiangjun Zhou, Ucheor B Choi, Ying Lai
Recent structural and functional studies of the synaptic vesicle fusion machinery suggest an inhibited tripartite complex consisting of neuronal soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs), synaptotagmin, and complexin prior to Ca2+ -triggered synaptic vesicle fusion. We speculate that Ca2+ -triggered fusion commences with the release of inhibition by Ca2+ binding to synaptotagmin C2 domains. Subsequently, fusion is assisted by SNARE complex zippering and by active membrane remodeling properties of synaptotagmin...
April 26, 2018: Trends in Cell Biology
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