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https://www.readbyqxmd.com/read/28546428/the-myocardin-related-transcription-factor-mkl-co-regulates-the-cellular-levels-of-two-profilin-isoforms
#1
Marion Joy, David Gau, Nevin Castellucci, Ron Prywes, Partha Roy
Megakaryoblastic leukemia (MKL)/ serum response factor (SRF)-mediated gene transcription is a highly conserved mechanism that connects dynamic reorganization of the actin cytoskeleton to regulation of expression of a wide range of genes including SRF itself and many important structural and regulatory components of actin cytoskeleton. In this study, we examined the possible role of MKL/SRF in the context of regulation of profilin (Pfn), a major controller of actin dynamics and actin cytoskeletal remodeling in cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545854/transcriptome-wide-identification-of-host-genes-targeted-by-tomato-spotted-wilt-virus-derived-small-interfering-rnas
#2
Shunmugiah V Ramesh, Sarah Williams, Madhu Kappagantu, Neena Mitter, Hanu R Pappu
RNA silencing mechanism functions as a major defense against invading viruses. The caveat in the RNA silencing mechanism is that the effector small interfering RNAs (siRNAs) act on any RNA transcripts with sequence complementarity irrespective of target's origin. A subset of highly expressed viral small interfering RNAs (vsiRNAs) derived from the tomato spotted wilt virus (TSWV; Tospovirus: Bunyaviridae) genome was analyzed for their propensity to downregulate the tomato transcriptome. A total of 11898 putative target sites on tomato transcripts were found to exhibit a propensity for down regulation by TSWV-derived vsiRNAs...
May 22, 2017: Virus Research
https://www.readbyqxmd.com/read/28539409/spatial-analysis-of-cdc42-activity-reveals-a-role-for-plasma-membrane-associated-cdc42-in-centrosome-regulation
#3
Kari A Herrington, Andrew L Trinh, Carolyn Dang, Ellen O'Shaughnessy, Klaus M Hahn, Enrico Gratton, Michelle A Digman, Christine Sütterlin
The ability of the small GTPase Cdc42 to regulate diverse cellular processes depends on tight spatial control of its activity. Cdc42 function is best understood at the plasma membrane (PM), where it regulates cytoskeletal organization and cell polarization. Active Cdc42 has also been detected at the Golgi, but its role and regulation at this organelle is only partially understood. Here we analyze the spatial distribution of Cdc42 activity by monitoring the dynamics of the Cdc42 FLARE biosensor using the phasor approach to FLIM-FRET...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539408/temporal-regulation-of-epithelium-formation-mediated-by-foxa-mklp1-mgcracgap-and-par-6
#4
Stephen E Von Stetina, Jennifer Liang, Georgios Marnellos, Susan E Mango
To establish the animal body plan, embryos link the external epidermis to the internal digestive tract. In Caenorhabditis elegans, this linkage is achieved by the Arcade Cells, which form an epithelial bridge between the foregut and epidermis, but little is known about how development of these three epithelia is coordinated temporally. The Arcade Cell epithelium is generated after the epidermis and digestive tract epithelia have matured, ensuring that both organs can withstand the mechanical stress of embryo elongation; mis-timing of epithelium formation leads to defects in morphogenesis...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539337/altered-expression-and-modulation-of-the-two-pore-domain-k2p-mechano-gated-potassium-channel-trek-1-in-overactive-human-detrusor
#5
Ricardo H Pineda, Balachandar Nedumaran, Joseph A Hypolite, Xiao-Qing Pan, Shandra Wilson, Randall B Meacham, Anna P Malykhina
Background Detrusor overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. The mechanisms of bladder smooth muscle compliance upon the wall stretch are poorly understood. We previously reported that the function of normal detrusor is regulated by TREK-1, a member of the mechano-gated subfamily of two-pore domain potassium (K2P) channels. In the present study, we aimed to identify the changes in expression and function of TREK-1 channels under pathological conditions associated with DO, evaluate the potential relationship between TREK-1 channels and cytoskeletal proteins in the human bladder, and test the possibility of modulation of TREK-1 channel expression by small RNAs...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#6
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28531660/carbon-black-aggregates-cause-endothelial-dysfunction-by-activating-rock
#7
Junyan Yan, Chia-Hsiang Lai, Shih-Chun Candice Lung, Wen-Cheng Wang, Chih-Ching Huang, Guan-Wen Chen, Guangli Suo, Cheng-Tai Choug, Chia-Hua Lin
Carbon black nanoparticles (CBNs) have been associated with the progression of atherosclerosis. CBNs normally enter the bloodstream and crosslink together to form agglomerates. However, most studies have used nano-sized CB particles to clarify the involvement of CBN exposure in CBN-induced endothelial dysfunction. Herein, we studied endothelial toxicity of CBN aggregates (CBA) to human EA.hy926 vascular cells. Cell viability, lactate dehydrogenase leakage, and oxidative stress were affected by the highest concentration of CBA...
May 15, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28529621/hoxa5-and-p53-cooperate-to-suppress-lung-cancer-cell-invasion-and-serve-as-good-prognostic-factors-in-non-small-cell-lung-cancer
#8
Chi-Jen Chang, Yen-Lin Chen, Chia-Hung Hsieh, Ya-Jung Liu, Sung-Liang Yu, Jeremy J W Chen, Chi-Chung Wang
Lung cancer is the leading cause of cancer mortality worldwide and tumor metastasis is the major cause of cancer-related death. Our previous study suggested that Homeobox A5 (HOXA5) could inhibit lung cancer cell invasion via regulating cytoskeletal remodeling and involved in tumor metastasis. Recently, consensus HOX binding sites was found in the p53 gene promoter region. However, whether the HOXA5 could cooperate with p53 and contribute the inhibition of lung cancer cell invasion is still unclear. The aim of the current study is to elucidate the correlation of HOXA5 and p53 in tumor invasion and its prognostic influence in lung cancer patient specimens...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28522589/identification-of-cancer-targeted-tropomyosin-inhibitors-and-their-synergy-with-microtubule-drugs
#9
Mark A Currier, Justine R Stehn, Ashleigh Swain, Duo Chen, Jeff Hook, Eleanor Eiffe, Andrew Heaton, David Brown, Brooke Nartker, David W Eaves, Nina Kloss, Herbert Treutlein, Jun Zeng, Irina B Alieva, Vera B Dugina, Edna C Hardeman, Peter W Gunning, Timothy P Cripe
Actin filaments, with their associated tropomyosin polymers, and microtubules are dynamic cytoskeletal systems regulating numerous cell functions. While anti-microtubule drugs are well-established, anti-actin drugs have been more elusive. We previously targeted actin in cancer cells by inhibiting the function of a tropomyosin isoform enriched in cancer cells, Tpm3.1, using a first-in-class compound, TR100. Here, we screened over 200 other anti-tropomyosin analogues for anti-cancer and on-target activity using a series of in vitro cell-based and biochemical assays...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28515282/talin-plays-a-critical-role-in-the-maintenance-of-the-regulatory-t-cell-pool
#10
Jane E Klann, Kelly A Remedios, Stephanie H Kim, Patrick J Metz, Justine Lopez, Lauren A Mack, Ye Zheng, Mark H Ginsberg, Brian G Petrich, John T Chang
Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28512143/diverse-roles-of-guanine-nucleotide-exchange-factors-in-regulating-collective-cell-migration
#11
Assaf Zaritsky, Yun-Yu Tseng, M Angeles Rabadán, Shefali Krishna, Michael Overholtzer, Gaudenz Danuser, Alan Hall
Efficient collective migration depends on a balance between contractility and cytoskeletal rearrangements, adhesion, and mechanical cell-cell communication, all controlled by GTPases of the RHO family. By comprehensive screening of guanine nucleotide exchange factors (GEFs) in human bronchial epithelial cell monolayers, we identified GEFs that are required for collective migration at large, such as SOS1 and β-PIX, and RHOA GEFs that are implicated in intercellular communication. Down-regulation of the latter GEFs differentially enhanced front-to-back propagation of guidance cues through the monolayer and was mirrored by down-regulation of RHOA expression and myosin II activity...
May 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28509555/differential-phosphoproteomic-analysis-of-recombinant-chinese-hamster-ovary-cells-following-temperature-shift
#12
Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis and signal transduction. However, to date little work has been carried out on the phosphoproteome in CHO cells. In this study we have carried out a large scale differential phosphoproteomic analysis of recombinant CHO cells following a reduction of culture temperature (temperature shift)...
May 16, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28508825/abcs-of-rhogtpases-indicating-potential-role-as-oncotargets
#13
REVIEW
Indira Bora, Neeta Shrivastava
RhoGTPases also known as molecular switches represent a family of GTP-binding proteins. They shuttle between "On" and "Off" states. In the "On" state, they activate plethora of molecules. These proteins perform a wide variety of functions involving cytoskeletal modeling, cell motility, migration, and mitosis. Members of this family are referred as master regulators of many cellular activities. Due to wide variety of portfolios attributed to RhoGTPases, their misbehavior leads to initiation and also progression of metastatic cancers...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28508358/degradomics-in-neurotrauma-profiling-traumatic-brain-injury
#14
Hadi Abou-El-Hassan, Fares Sukhon, Edwyn Jeremy Assaf, Hisham Bahmad, Hussein Abou-Abbass, Hussam Jourdi, Firas H Kobeissy
Degradomics has recently emerged as a subdiscipline in the omics era with a focus on characterizing signature breakdown products implicated in various disease processes. Driven by promising experimental findings in cancer, neuroscience, and metabolomic disorders, degradomics has significantly promoted the notion of disease-specific "degradome." A degradome arises from the activation of several proteases that target specific substrates and generate signature protein fragments. Several proteases such as calpains, caspases, cathepsins, and matrix metalloproteinases (MMPs) are involved in the pathogenesis of numerous diseases that disturb the physiologic balance between protein synthesis and protein degradation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28502042/tale-of-the-good-and-the-bad-cdk5-remodeling-of-the-actin-cytoskeleton-in-the-brain
#15
REVIEW
Kavita Shah, Sandra Rossie
Cdk5 kinase, a cyclin-dependent kinase family member, is a key regulator of cytoskeletal remodeling in the brain. Cdk5 is essential for brain development during embryogenesis. After birth, it is essential for numerous neuronal processes such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity is deregulated in various brain disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and ischemic stroke, resulting in profound remodeling of the neuronal cytoskeleton, loss of synapses, and ultimately neurodegeneration...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28500524/cytoskeletal-proteins-in-caulobacter-crescentus-spatial-orchestrators-of-cell-cycle-progression-development-and-cell-shape
#16
Kousik Sundararajan, Erin D Goley
Caulobacter crescentus, an aquatic Gram-negative α-proteobacterium, is dimorphic, as a result of asymmetric cell divisions that give rise to a free-swimming swarmer daughter cell and a stationary stalked daughter. Cell polarity of vibrioid C. crescentus cells is marked by the presence of a stalk at one end in the stationary form and a polar flagellum in the motile form. Progression through the cell cycle and execution of the associated morphogenetic events are tightly controlled through regulation of the abundance and activity of key proteins...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28500522/e-coli-cell-cycle-machinery
#17
Joe Lutkenhaus, Shishen Du
Cytokinesis in E. coli is organized by a cytoskeletal element designated the Z ring. The Z ring is formed at midcell by the coalescence of FtsZ filaments tethered to the membrane by interaction of FtsZ's conserved C-terminal peptide (CCTP) with two membrane-associated proteins, FtsA and ZipA. Although interaction between an FtsZ monomer and either of these proteins is of low affinity, high affinity is achieved through avidity - polymerization linked CCTPs interacting with the membrane tethers. The placement of the Z ring at midcell is ensured by antagonists of FtsZ polymerization that are positioned within the cell and target FtsZ filaments through the CCTP...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28500272/probing-the-lithium-response-pathway-in-hipscs-implicates-the-phosphoregulatory-set-point-for-a-cytoskeletal-modulator-in-bipolar-pathogenesis
#18
Brian T D Tobe, Andrew M Crain, Alicia M Winquist, Barbara Calabrese, Hiroko Makihara, Wen-Ning Zhao, Jasmin Lalonde, Haruko Nakamura, Glenn Konopaske, Michelle Sidor, Cameron D Pernia, Naoya Yamashita, Moyuka Wada, Yuuka Inoue, Fumio Nakamura, Steven D Sheridan, Ryan W Logan, Michael Brandel, Dongmei Wu, Joshua Hunsberger, Laurel Dorsett, Cordulla Duerr, Ranor C B Basa, Michael J McCarthy, Namrata D Udeshi, Philipp Mertins, Steven A Carr, Guy A Rouleau, Lina Mastrangelo, Jianxue Li, Gustavo J Gutierrez, Laurence M Brill, Nikolaos Venizelos, Guang Chen, Jeffrey S Nye, Husseini Manji, Jeffrey H Price, Colleen A McClung, Hagop S Akiskal, Martin Alda, De-Maw M Chuang, Joseph T Coyle, Yang Liu, Yang D Teng, Toshio Ohshima, Katsuhiko Mikoshiba, Richard L Sidman, Shelley Halpain, Stephen J Haggarty, Yoshio Goshima, Evan Y Snyder
The molecular pathogenesis of bipolar disorder (BPD) is poorly understood. Using human-induced pluripotent stem cells (hiPSCs) to unravel such mechanisms in polygenic diseases is generally challenging. However, hiPSCs from BPD patients responsive to lithium offered unique opportunities to discern lithium's target and hence gain molecular insight into BPD. By profiling the proteomics of BDP-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2)...
May 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28495532/new-insights-into-the-role-of-mitochondrial-calcium-homeostasis-in-cell-migration
#19
Vincent Paupe, Julien Prudent
Mitochondria are dynamic organelles involved in numerous physiological functions. Beyond their function in ATP production, mitochondria regulate cell death, reactive oxygen species (ROS) generation, immunity and metabolism. Mitochondria also play a key role in the buffering of cytosolic calcium, and calcium transported into the matrix regulates mitochondrial metabolism. Recently, the identification of the mitochondrial calcium uniporter (MCU) and associated regulators has allowed the characterization of new physiological roles for calcium in both mitochondrial and cellular homeostasis...
May 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28495495/translating-in-vitro-ligand-bias-into-in-vivo-efficacy
#20
REVIEW
Louis M Luttrell, Stuart Maudsley, Diane Gesty-Palmer
It is increasingly apparent that ligand structure influences both the efficiency with which G protein-coupled receptors (GPCRs) engage their downstream effectors and the manner in which they are activated. Thus, 'biased' agonists, synthetic ligands whose intrinsic efficacy differs from the native ligand, afford a strategy for manipulating GPCR signaling in ways that promote beneficial signals while blocking potentially deleterious ones. Still, there are significant challenges in relating in vitro ligand efficacy, which is typically measured in heterologous expression systems, to the biological response in vivo, where the ligand is acting on natively expressed receptors and in the presence of the endogenous ligand...
May 7, 2017: Cellular Signalling
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