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https://www.readbyqxmd.com/read/28298491/cyk-4-regulates-rac-but-not-rho-during-cytokinesis
#1
Yelena Zhuravlev, Sophia M Hirsch, Shawn N Jordan, Julien Dumont, Mimi Shirasu-Hiza, Julie C Canman
Cytokinesis is driven by constriction of an actomyosin contractile ring that is controlled by Rho family small GTPases. Rho, activated by the Guanine-nucleotide Exchange Factor (GEF) ECT-2, is upstream of both myosin-II activation and diaphanous formin-mediated filamentous actin (f-actin) assembly, which drive ring constriction. The role for Rac and its regulators is more controversial but, based on the finding that Rac inactivation can rescue cytokinesis failure when the GTPase Activating Protein (GAP) CYK-4 is disrupted, Rac activity was proposed to be inhibitory to contractile ring constriction and thus specifically inactivated by CYK-4 at the division plane...
March 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28263325/genome-wide-mapping-of-long-range-contacts-unveils-clustering-of-dna-double-strand-breaks-at-damaged-active-genes
#2
François Aymard, Marion Aguirrebengoa, Emmanuelle Guillou, Biola M Javierre, Beatrix Bugler, Coline Arnould, Vincent Rocher, Jason S Iacovoni, Anna Biernacka, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Peter Fraser, Gaëlle Legube
The ability of DNA double-strand breaks (DSBs) to cluster in mammalian cells has been a subject of intense debate in recent years. Here we used a high-throughput chromosome conformation capture assay (capture Hi-C) to investigate clustering of DSBs induced at defined loci in the human genome. The results unambiguously demonstrated that DSBs cluster, but only when they are induced within transcriptionally active genes. Clustering of damaged genes occurs primarily during the G1 cell-cycle phase and coincides with delayed repair...
March 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28256237/two-distinct-actin-networks-mediate-traction-oscillations-to-confer-focal-adhesion-mechanosensing
#3
Zhanghan Wu, Sergey V Plotnikov, Abdiwahab Y Moalim, Clare M Waterman, Jian Liu
Focal adhesions (FAs) are integrin-based transmembrane assemblies that connect a cell to its extracellular matrix (ECM). They are mechanosensors through which cells exert actin cytoskeleton-mediated traction forces to sense the ECM stiffness. Interestingly, FAs themselves are dynamic structures that adapt their growth in response to mechanical force. It is unclear how the cell manages the plasticity of the FA structure and the associated traction force to accurately sense ECM stiffness. Strikingly, FA traction forces oscillate in time and space, and govern the cell mechanosensing of ECM stiffness...
February 28, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28255515/microarrays-enabled-hypothesis-generation-the-suspect-role-of-fnbp-1-in-neuropsychiatric-pathogenesis-associated-with-hiv-and-or-hcv-infection
#4
A Katsounas, K R Wilting, R A Lempicki, J F Schlaak, G Gerken
OBJECTIVE: The spectrum of neuropsychiatric illness (NI) associated with the Human Immunodeficiency Virus (HIV) and/or the Hepatitis C Virus (HCV) is far reaching and significantly impacts the clinical presentation and outcome of infected persons; however, the etiological and pathophysiological background remains partially understood. The present work was aimed to investigate the potential significance of formin binding protein 1 (FNBP-1)-dependent pathways in NI-pathogenesis by elaborating on previous microarray-based research in HIV and/or HCV-infected patients receiving interferon-α (IFN-α) immunotherapy via a rigorous data mining procedure...
December 2016: Journal of AIDS & Clinical Research
https://www.readbyqxmd.com/read/28255013/histone-deacetylase-6-regulates-cytokinesis-and-erythrocyte-enucleation-through-deacetylation-of-formin-protein-mdia2
#5
Xuehui Li, Yang Mei, Bowen Yan, Eric Vitriol, Suming Huang, Peng Ji, Yi Qiu
The formin mDia2 plays a critical role in a number of cellular processes through its ability to promote nucleation and elongation of actin filaments. In erythroblasts, this includes control of cytokinesis and enucleation by regulating contractile actin ring formation. Here, we report a novel mechanism of how mDia2 is regulated: through acetylation and deacetylation at lysine 970 in formin homology 2 domain. Ectopic expression of an acetyl-mimic mDia2 mutant in mouse erythroblasts is sufficient to abolish contractile actin ring formation at the cleavage furrow and subsequent erythrocyte cytokinesis and enucleation...
March 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28238662/coordination-by-cdc42-of-actin-contractility-and-adhesion-for-melanoblast-movement-in-mouse-skin
#6
Emma F Woodham, Nikki R Paul, Benjamin Tyrrell, Heather J Spence, Karthic Swaminathan, Michelle R Scribner, Evangelos Giampazolias, Ann Hedley, William Clark, Frieda Kage, Daniel J Marston, Klaus M Hahn, Stephen W G Tait, Lionel Larue, Cord H Brakebusch, Robert H Insall, Laura M Machesky
The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin...
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28231467/synaptic-vesicle-endocytosis-occurs-on-multiple-timescales-and-is-mediated-by-formin-dependent-actin-assembly
#7
Tolga Soykan, Natalie Kaempf, Takeshi Sakaba, Dennis Vollweiter, Felix Goerdeler, Dmytro Puchkov, Natalia L Kononenko, Volker Haucke
Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Recent data suggest that at physiological temperature SVs are internalized via clathrin-independent ultrafast endocytosis (UFE) within hundreds of milliseconds, while other studies have postulated a key role for clathrin-mediated endocytosis (CME) of SV proteins on a timescale of seconds to tens of seconds. Here we demonstrate using cultured hippocampal neurons as a model that at physiological temperature SV endocytosis occurs on several timescales from less than a second to several seconds, yet, is largely independent of clathrin...
February 22, 2017: Neuron
https://www.readbyqxmd.com/read/28198387/high-fmnl3-expression-promotes-nasopharyngeal-carcinoma-cell-metastasis-role-in-tgf-%C3%AE-1-induced-epithelia-to-mesenchymal-transition
#8
Yanxia Wu, Zhihua Shen, Keke Wang, Yanping Ha, Hong Lei, Yanan Jia, Ranran Ding, Dongmei Wu, Siyuan Gan, Rujia Li, Botao Luo, Hanguo Jiang, Wei Jie
Formin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28183815/proteomic-screen-for-cellular-targets-of-the-vaccinia-virus-f10-protein-kinase-reveals-that-phosphorylation-of-mdia-regulates-stress-fiber-formation
#9
Matthew D Greseth, Dominique M Carter, Scott S Terhune, Paula Traktman
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. While this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28183700/2016-atvb-plenary-lecture-receptor-for-advanced-glycation-endproducts-and-implications-for-the-pathogenesis-an-treatment-of-cardiometabolic-disorders-spotlight-on-the-macrophage
#10
REVIEW
Ann Marie Schmidt
The receptor for advanced glycation endproducts (RAGE) interacts with a unique repertoire of ligands that form and collect in the tissues and circulation in diabetes mellitus, aging, inflammation, renal failure, and obesity. RAGE is expressed on multiple cell types linked to tissue perturbation in these settings. This brief review focuses on the role of RAGE in monocytes/macrophages and how RAGE ligand engagement on these cells mediates seminal changes in monocyte/macrophage migration, oxidative stress, cholesterol efflux, and pro- versus anti-inflammatory cues that signal to tissue damage...
February 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28145526/zp3-is-required-for-germinal-vesicle-breakdown-in-mouse-oocyte-meiosis
#11
Lei-Lei Gao, Chun-Xiang Zhou, Xiao-Lan Zhang, Peng Liu, Zhen Jin, Gang-Yi Zhu, Yang Ma, Jing Li, Zhi-Xia Yang, Dong Zhang
ZP3 is a principal component of the zona pellucida (ZP) of mammalian oocytes and is essential for normal fertility, and knockout of ZP3 causes complete infertility. ZP3 promotes fertilization by recognizing sperm binding and activating the acrosome reaction; however, additional cellular roles for ZP3 in mammalian oocytes have not been yet reported. In the current study, we found that ZP3 was strongly expressed in the nucleus during prophase and gradually translocated to the ZP. Knockdown of ZP3 by a specific siRNA dramatically inhibited germinal vesicle breakdown (GVBD) (marking the beginning of meiosis), significantly reducing the percentage of MII oocytes...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128308/%C3%AE-v-class-integrins-exert-dual-roles-on-%C3%AE-5%C3%AE-1-integrins-to-strengthen-adhesion-to-fibronectin
#12
Mitasha Bharadwaj, Nico Strohmeyer, Georgina P Colo, Jonne Helenius, Niko Beerenwinkel, Herbert B Schiller, Reinhard Fässler, Daniel J Müller
Upon binding to the extracellular matrix protein, fibronectin, αV-class and α5β1 integrins trigger the recruitment of large protein assemblies and strengthen cell adhesion. Both integrin classes have been functionally specified, however their specific roles in immediate phases of cell attachment remain uncharacterized. Here, we quantify the adhesion of αV-class and/or α5β1 integrins expressing fibroblasts initiating attachment to fibronectin (≤120 s) by single-cell force spectroscopy. Our data reveals that αV-class integrins outcompete α5β1 integrins...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28115158/mdia2-and-cxcl12-cxcr4-chemokine-signaling-intersect-to-drive-tumor-cell-amoeboid-morphological-transitions
#13
Meghan M Wyse, Silvia Goicoechea, Rafael Garcia-Mata, Andrea L Nestor-Kalinoski, Kathryn M Eisenmann
Morphological plasticity in response to environmental cues in migrating cancer cells requires F-actin cytoskeletal rearrangements. Conserved formin family proteins play critical roles in cell shape, tumor cell motility, invasion and metastasis, in part, through assembly of non-branched actin filaments. Diaphanous-related formin-2 (mDia2/Diaph3/Drf3/Dia) regulates mesenchymal-to-amoeboid morphological conversions and non-apoptotic blebbing in tumor cells by interacting with its inhibitor diaphanous-interacting protein (DIP), and disrupting cortical F-actin assembly and bundling...
March 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28114270/long-range-self-organization-of-cytoskeletal-myosin-ii-filament-stacks
#14
Shiqiong Hu, Kinjal Dasbiswas, Zhenhuan Guo, Yee-Han Tee, Visalatchi Thiagarajan, Pascal Hersen, Teng-Leong Chew, Samuel A Safran, Ronen Zaidel-Bar, Alexander D Bershadsky
Although myosin II filaments are known to exist in non-muscle cells, their dynamics and organization are incompletely understood. Here, we combined structured illumination microscopy with pharmacological and genetic perturbations, to study the process of actomyosin cytoskeleton self-organization into arcs and stress fibres. A striking feature of the myosin II filament organization was their 'registered' alignment into stacks, spanning up to several micrometres in the direction orthogonal to the parallel actin bundles...
February 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28092406/llfh1-mediated-interaction-between-actin-fringe-and-exocytic-vesicles-is-involved-in-pollen-tube-tip-growth
#15
Shanwei Li, Huaijian Dong, Weike Pei, Chaonan Liu, Sha Zhang, Tiantian Sun, Xiuhua Xue, Haiyun Ren
Pollen tube tip growth is an extreme form of polarized cell growth, which requires polarized exocytosis based on a dynamic actin cytoskeleton. However, the molecular basis for the connection between actin filaments and exocytic vesicles is unclear. Here, we identified a Lilium longiflorum pollen-specific formin (LlFH1) and found that it localized at the apical vesicles and plasma membrane (PM). Overexpression of LlFH1 induced excessive actin cables in the tube tip region, and downregulation of LlFH1 eliminated the actin fringe...
January 16, 2017: New Phytologist
https://www.readbyqxmd.com/read/28089989/rhoa-regulates-actin-network-dynamics-during-apical-surface-emergence-in-multiciliated-epithelial-cells
#16
Jakub Sedzinski, Edouard Hannezo, Fan Tu, Maté Biro, John B Wallingford
Homeostatic replacement of epithelial cells from basal precursors is a multistep process involving progenitor cell specification, radial intercalation and, finally, apical surface emergence. Recent data demonstrate that actin-based pushing under the control of the formin protein Fmn1 drives apical emergence in nascent multiciliated epithelial cells (MCCs), but little else is known about this actin network or the control of Fmn1. Here, we explore the role of the small GTPase RhoA in MCC apical emergence. Disruption of RhoA function reduced the rate of apical surface expansion and decreased the final size of the apical domain...
January 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28058271/remodeling-of-the-inner-hair-cell-microtubule-meshwork-in-a-mouse-model-of-auditory-neuropathy-auna1
#17
Clément Surel, Marie Guillet, Marc Lenoir, Jérôme Bourien, Gaston Sendin, Willy Joly, Benjamin Delprat, Marci M Lesperance, Jean-Luc Puel, Régis Nouvian
Auditory neuropathy 1 (AUNA1) is a form of human deafness resulting from a point mutation in the 5' untranslated region of the Diaphanous homolog 3 (DIAPH3) gene. Notably, the DIAPH3 mutation leads to the overexpression of the DIAPH3 protein, a formin family member involved in cytoskeleton dynamics. Through study of diap3-overexpressing transgenic (Tg) mice, we examine in further detail the anatomical, functional, and molecular mechanisms underlying AUNA1. We identify diap3 as a component of the hair cells apical pole in wild-type mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28057602/formin-like-1-expression-is-increased-on-cd4-t-lymphocytes-in-spontaneous-autoimmune-uveitis
#18
Roxane L Degroote, Patrizia B Uhl, Barbara Amann, Angela M Krackhardt, Marius Ueffing, Stefanie M Hauck, Cornelia A Deeg
The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases...
February 10, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28003573/a-novel-missense-variant-in-the-diaph1-gene-in-a-korean-family-with-autosomal-dominant-nonsyndromic-hearing-loss
#19
Tae-Hun Kang, Jeong-In Baek, Borum Sagong, Hong-Joon Park, Chan Ik Park, Kyu-Yup Lee, Un-Kyung Kim
Hair cells in the cochlea display highly regulated actin polymerization, which is mediated by the human diaphanous-related formin 1 gene (DIAPH1; also called DFNA1, DIA1). DFNA1, the first type of autosomal dominant nonsyndromic hearing loss (ADNSHL), is known to be associated with mutations in DIAPH1. However, no genetic study of DFNA1 in Koreans with hearing loss has yet been reported. A 51-year-old patient in a Korean family with ADNSHL was examined by pure-tone audiometry, and genetic analysis of DIAPH1 was performed...
December 21, 2016: Genes & Genetic Systems
https://www.readbyqxmd.com/read/27974406/thrombotic-microangiopathy-in-inverted-formin-2-mediated-renal-disease
#20
Rachel C Challis, Troels Ring, Yaobo Xu, Edwin K S Wong, Oliver Flossmann, Ian S D Roberts, Saeed Ahmed, Michael Wetherall, Giedrius Salkus, Vicky Brocklebank, Julian Fester, Lisa Strain, Valerie Wilson, Katrina M Wood, Kevin J Marchbank, Mauro Santibanez-Koref, Timothy H J Goodship, David Kavanagh
The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab...
December 14, 2016: Journal of the American Society of Nephrology: JASN
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