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https://www.readbyqxmd.com/read/28303963/structural-analysis-of-human-cofilin-2-filamentous-actin-assemblies-atomic-resolution-insights-from-magic-angle-spinning-nmr-spectroscopy
#1
Jenna Yehl, Elena Kudryashova, Emil Reisler, Dmitri Kudryashov, Tatyana Polenova
Cellular actin dynamics is an essential element of numerous cellular processes, such as cell motility, cell division and endocytosis. Actin's involvement in these processes is mediated by many actin-binding proteins, among which the cofilin family plays unique and essential role in accelerating actin treadmilling in filamentous actin (F-actin) in a nucleotide-state dependent manner. Cofilin preferentially interacts with older filaments by recognizing time-dependent changes in F-actin structure associated with the hydrolysis of ATP and release of inorganic phosphate (Pi) from the nucleotide cleft of actin...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28300846/regulation-of-rhoa-activity-by-the-cellular-prion-protein
#2
Hee-Jun Kim, Hong-Seok Choi, Jeong-Ho Park, Mo-Jong Kim, Hyoung-Gon Lee, Robert Bob Petersen, Yong-Sun Kim, Jae-Bong Park, Eun-Kyoung Choi
The cellular prion protein (PrP(C)) is a highly conserved glycosylphosphatidylinositol (GPI)-anchored membrane protein that is involved in the signal transduction during the initial phase of neurite outgrowth. The Ras homolog gene family member A (RhoA) is a small GTPase that is known to have an essential role in regulating the development, differentiation, survival, and death of neurons in the central nervous system. Although recent studies have shown the dysregulation of RhoA in a variety of neurodegenerative diseases, the role of RhoA in prion pathogenesis remains unclear...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28293874/diversity-of-actin-architecture-in-human-osteoclasts-network-of-curved-and-branched-actin-supporting-cell-shape-and-intercellular-micrometer-level-tubes
#3
Paula Pennanen, Maria Helena Alanne, Elnaz Fazeli, Takahiro Deguchi, Tuomas Näreoja, Sirkku Peltonen, Juha Peltonen
Osteoclasts are multinucleated bone-resorbing cells with a dynamic actin cytoskeleton. Osteoclasts are derived from circulating mononuclear precursors. Confocal and stimulated emission depletion (STED) super-resolution microscopy was used to investigate peripheral blood-derived human osteoclasts cultured on glass surfaces. STED and confocal microscopy demonstrated that the actin was curved and branched, for instance, in the vicinity of membrane ruffles. The overall architecture of the curved actin network extended from the podosomes to the top of the cell...
March 14, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28282023/competition-between-tropomyosin-fimbrin-and-adf-cofilin-drives-their-sorting-to-distinct-actin-filament-networks
#4
Jenna R Christensen, Glen M Hocky, Kaitlin E Homa, Alisha N Morganthaler, Sarah E Hitchcock-DeGregori, Gregory A Voth, David R Kovar
The fission yeast actin cytoskeleton is an ideal, simplified system to investigate fundamental mechanisms behind cellular self-organization. By focusing on the stabilizing protein tropomyosin Cdc8, bundling protein fimbrin Fim1, and severing protein coffin Adf1, we examined how their pairwise and collective interactions with actin filaments regulate their activity and segregation to functionally diverse F-actin networks. Utilizing multi-color TIRF microscopy of in vitro reconstituted F-actin networks, we observed and characterized two distinct Cdc8 cables loading and spreading cooperatively on individual actin filaments...
March 10, 2017: ELife
https://www.readbyqxmd.com/read/28274853/identification-of-sennoside-a-as-a-novel-inhibitor-of-the-slingshot-ssh-family-proteins-related-to-cancer-metastasis
#5
Seon Young Lee, Wooil Kim, Young Geun Lee, Hyo Jin Kang, Sang-Hyun Lee, Sun Young Park, Jeong-Ki Min, Sang-Rae Lee, Sang J Chung
Phospho-cofilin (p-cofilin), which has a phosphate group on Ser-3, is involved in actin polymerization. Its dephosphorylated form promotes filopodia formation and cell migration by enhancing actin depolymerization. Protein phosphatase slingshot homologs (SSHs), known as dual-specificity phosphatases, catalyze hydrolytic removal of the Ser-3 phosphate group from phospho-cofilin. Aberrant SSH activity results in cancer metastasis, implicating SSHs as potential therapeutic targets for cancer metastasis. In this study, we screened 658 natural products purified from traditional oriental medicinal plants to identify three potent SSH inhibitors with submicromolar or single-digit micromolar Ki values: gossypol, hypericin, and sennoside A...
March 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28270556/cytoskeletal-adaptivity-regulates-t-cell-receptor-signaling
#6
Timothy J Thauland, Kenneth H Hu, Marc A Bruce, Manish J Butte
The factors that govern T cell activation control the initiation and progression of adaptive immune responses. T cells recognize their cognate antigen on the surface of antigen-presenting cells (APCs) through the T cell receptor, which results in the formation of a contact region (immune synapse) between the two cells and the activation of the T cells. Activated T cells proliferate and differentiate into effector T cells that secrete cytokines, provide help to B cells, and kill target cells. We asked whether the actin cytoskeleton governs differences in signaling in effector T cells versus naïve (unstimulated) T cells...
March 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/28242433/the-tired-hippocampus-the-molecular-impact-of-sleep-deprivation-on-hippocampal-function
#7
REVIEW
Robbert Havekes, Ted Abel
Memory consolidation, the process by which information is stored following training, consists of synaptic consolidation and systems consolidation. It is widely acknowledged that sleep deprivation has a profound effect on synaptic consolidation, particularly for memories that require the hippocampus. It is unclear, however, which of the many molecular changes associated with sleep deprivation directly contribute to memory deficits. In this review, we highlight recent studies showing that sleep deprivation impairs hippocampal cAMP and mTOR signaling, and ultimately causes spine loss in CA1 neurons in a cofilin-dependent fashion...
February 27, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28237967/heterozygous-vangl2-looptail-mice-reveal-novel-roles-for-the-planar-cell-polarity-pathway-in-adult-lung-homeostasis-and-repair
#8
Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Miguel Pereira, Nina Y Gross, Akmol Ali, Maria Kolatsi-Joannou, Marjo-Riitta Jarvelin, Juha Pekkanen, Eugenia Papakrivopoulou, David A Long, Mark Griffiths, Darcy Wagner, Melanie Königshoff, Matthew Hind, Cosetta Minelli, Clare M Lloyd, Charlotte H Dean
Lung diseases impose a huge economic and health burden worldwide. A key aspect of several adult lung diseases, such as Idiopathic pulmonary fibrosis (IPF) and Chronic Obstructive pulmonary Disease (COPD), including emphysema, is aberrant tissue repair, which leads to an accumulation of damage and impaired respiratory function. Currently, there are few effective treatments available for these diseases and their incidence is rising.The Planar Cell Polarity (PCP) pathway is critical for the embryonic development of many organs, including kidney and lung...
February 24, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28216317/tropomyosin-isoforms-specify-functionally-distinct-actin-filament-populations-in%C3%A2-vitro
#9
Gergana Gateva, Elena Kremneva, Theresia Reindl, Tommi Kotila, Konstantin Kogan, Laurène Gressin, Peter W Gunning, Dietmar J Manstein, Alphée Michelot, Pekka Lappalainen
Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins, including actin-depolymerizing factor (ADF)/cofilins and myosins, with actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes. Different isoforms display non-redundant functions and partially non-overlapping localization patterns, for example within the stress fiber network [6, 7]...
March 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28216224/targeted-proteomics-driven-verification-of-biomarker-candidates-associated-with-breast-cancer-aggressiveness
#10
Iva Procházková, Juraj Lenčo, Alena Fučíková, Jiří Dresler, Lenka Čápková, Roman Hrstka, Rudolf Nenutil, Pavel Bouchal
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28202517/tankyrase-binding-protein-tnks1bp1-regulates-actin-cytoskeleton-rearrangement-and-cancer-cell-invasion
#11
Tomokazu Ohishi, Haruka Yoshida, Masamichi Katori, Toshiro Migita, Yukiko Muramatsu, Mao Miyake, Yuichi Ishikawa, Akio Saiura, Shun-Ichiro Iemura, Tohru Natsume, Hiroyuki Seimiya
Tankyrase, a poly(ADP-ribose) polymerase (PARP) that promotes telomere elongation and Wnt/β-catenin signaling, has various binding partners, suggesting that it has as-yet unidentified functions. Here we report that the tankyrase-binding protein TNKS1BP1 regulates actin cytoskeleton and cancer cell invasion, which is closely associated with cancer progression. TNKS1BP1 colocalized with actin filaments and negatively regulated cell invasion. In TNKS1BP1-depleted cells, actin filament dynamics, focal adhesion, and lamellipodia ruffling were increased with activation of the ROCK-LIMK-cofilin pathway...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28194647/cofilin-mediates-lps-induced-microglial-cell-activation-and-associated-neurotoxicity-through-activation-of-nf-%C3%AE%C2%BAb-and-jak-stat-pathway
#12
Qasim Alhadidi, Zahoor A Shah
Microglial cells are activated in response to different types of injuries or stress in the CNS. Such activation is necessary to get rid of the injurious agents and restore tissue homeostasis. However, excessive activation of microglial cells is harmful and contributes to secondary injury. Pertinently, microglial cell activity was targeted in many preclinical and clinical studies but such strategy failed in clinical trials. The main reason behind the failed attempts is the complexity of the injury mechanisms which needs either a combination therapy or targeting a process that is involved in multiple pathways...
February 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28167682/the-rap1-cofilin-pathway-coordinates-actin-reorganization-and-mtoc-polarization-at-the-b-cell-immune-synapse
#13
Jia C Wang, Jeff Y-J Lee, Sonja Christian, May Dang-Lawson, Caitlin Pritchard, Spencer A Freeman, Michael R Gold
B cells that bind antigens displayed on antigen-presenting cells (APCs) form an immune synapse, a polarized cellular structure that optimizes the dual functions of the B-cell receptor (BCR), signal transduction and antigen internalization. Immune synapse formation involves polarization of the microtubule-organizing center (MTOC) towards the APC. We now show that BCR-induced MTOC polarization requires the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, as well as cofilin, an actin-severing protein that is regulated by Rap1...
February 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28162947/fty720-supplementation-partially-improves-erectile-dysfunction-in-rats-with-streptozotocin-induced-type-1-diabetes-through-inhibition-of-endothelial-dysfunction-and-corporal-fibrosis
#14
Kai Cui, Yajun Ruan, Tao Wang, Ke Rao, Zhong Chen, Shaogang Wang, Jihong Liu
INTRODUCTION: Erectile dysfunction (ED) in patients with diabetes mellitus (DM) seriously affects their quality of life. However, these patients show a poor effect rate for oral phosphodiesterase type 5 inhibitors. Thus, new treatment methods are urgently needed. Fingolimod hydrochloride (FTY720) was approved in 2010 for the treatment of patients with the relapsing-remitting form of multiple sclerosis. AIM: To investigate whether FTY720 supplementation could ameliorate ED induced by DM (DMED)...
February 2, 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28161904/immune-complex-level-of-cofilin-1-in-sera-is-associated-with-cancer-progression-and-poor-prognosis-in-pancreatic-cancer
#15
Mamoru Satoh, Shigetsugu Takano, Kazuyuki Sogawa, Kenta Noda, Hideyuki Yoshitomi, Masumi Ishibashi, Kaoru Mogushi, Hirotaka Takizawa, Masayuki Otsuka, Hiroaki Shimizu, Masaru Miyazaki, Fumio Nomura
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. To improve its outcome, the reliable biomarkers are urgently needed. In this study, we aimed to elucidate the key molecules involved in PDAC progression using proteomics approaches. First, we performed two-dimensional electrophoresis to identify the proteins overexpressed in PDAC tissues. Following the analysis of agarose gel spots, cofilin-1 were identified and verified as a candidate protein commonly upregulated in PDAC tissues...
February 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28152068/aerobic-exercise-regulates-rho-cofilin-pathways-to-rescue-synaptic-loss-in-aged-rats
#16
Yan Li, Li Zhao, Boya Gu, Jiajia Cai, Yuanyuan Lv, Laikang Yu
PURPOSE: The role of exercise to prevent or reverse aging-induced cognitive decline has been widely reported. This neuroprotection is associated with changes in the synaptic structure plasticity. However, the mechanisms of exercise-induced synaptic plasticity in the aging brain are still unclear. Thus, the aim of the present study is to investigate the aging-related alterations of Rho-GTPase and the modulatory influences of exercise training. METHODS: Young and old rats were used in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28147273/mir-182-regulates-slit2-mediated-axon-guidance-by-modulating-the-local-translation-of-a-specific-mrna
#17
Anaïs Bellon, Archana Iyer, Simone Bridi, Flora C Y Lee, Cesaré Ovando-Vázquez, Eloina Corradi, Sara Longhi, Michela Roccuzzo, Stephanie Strohbuecker, Sindhu Naik, Peter Sarkies, Eric Miska, Cei Abreu-Goodger, Christine E Holt, Marie-Laure Baudet
During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets of mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific mRNAs are selected for translation. MicroRNAs (miRNAs) are critical translational regulators that act through a sequence-specific mechanism. Here, we investigate the local role of miRNAs in mRNA-specific translation during pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28130864/complex-roles-of-annexin-a2-in-host-blood-brain-barrier-invasion-by-cryptococcus-neoformans
#18
Wei Fang, Zhen-Zong Fa, Qun Xie, Gui-Zhen Wang, Jiu Yi, Chao Zhang, Guang-Xun Meng, Ju-Lin Gu, Wan-Qing Liao
INTRODUCTION: Fungal transversal across the brain microvascular endothelial cells (BMECs) is the essential step for the development of cryptococcal meningoencephalitis. Annexin A2 (AnxA2) is an important signaling protein involved in several intracellular processes such as membrane trafficking, endocytosis, and exocytosis. AIM: To investigate the roles and mechanism of AnxA2 during cryptococcal transversal of BMECs. RESULTS: Cryptococcus neoformans infection initiated upregulation of AnxA2 in mouse BMECs...
January 28, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28126411/perfluorooctanoic-acid-affects-endocytosis-involving-clathrin-light-chain-a-and-microrna-133b-3p-in-mouse-testes
#19
Yin Lu, Jianshe Wang, Xuejiang Guo, Shengmin Yan, Jiayin Dai
Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28124604/the-interplay-between-cofilin-and-phospho-cofilin-its-role-in-maintaining-blood-brain-barrier-integrity
#20
Qasim Alhadidi, Muhammad Shahdaat Bin Sayeed, Zahoor Shah
The blood brain barrier (BBB) is a continuous, non-fenestrated vessel system that tightly regulates the movement of molecules, ions, and cells between the blood and the central nervous system. Endothelial cells are the major constituents of the BBB and these cells are linked to each other through intercellular contact points composed of tight junctions, adherent junctions and gap junctions. These three types of junctions are connected to the intracellular actin cytoskeleton via various adaptor proteins. Thus, the actin cytoskeleton plays a crucial role in regulating the stability of endothelial cell contacts and vascular permeability...
January 17, 2017: CNS & Neurological Disorders Drug Targets
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