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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
Beenu Moza Jalali, Pawel Likszo, Aneta Andronowska, Dariusz J Skarzynski
During early pregnancy, uterine epithelial cells undergo major transformations in their cytoskeleton that make the endometrium receptive for conceptus attachment. Actin binding proteins (ABPs) such as cofilin, gelsolin, and vinculin are involved in regulating actin polymerization, severing or crosslinking actin to integrins. However, whether ABPs are involved in epithelial remodeling or embryo adhesion in pigs is unknown. Therefore, the expression and distribution of these proteins were investigated in porcine endometrium on Days 10 and 13 (pre-implantation period), and 16 (attachment phase) of the estrous cycle or pregnancy...
May 8, 2018: Theriogenology
Hiroaki Mizuno, Kotaro Tanaka, Sawako Yamashiro, Akihiro Narita, Naoki Watanabe
The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin barely associates. In vitro, F-actin decorated with cofilin exhibits a marked increase in the filament twist. On the other hand, a mammalian formin mDia1 rotates along the long-pitch actin helix during processive actin elongation (helical rotation)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Georgios Tsinias, Sofia Nikou, Theodoros Papadas, Panagiotis Pitsos, Helen Papadaki, Vasiliki Bravou
Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Protein expressions of cofilin, N-WASP, α -parvin, β -parvin, and PINCH1 were examined by immunohistochemistry in 72 human laryngeal squamous cell carcinomas...
2018: Analytical Cellular Pathology (Amsterdam)
Jinyang Wang, Lei Zhang, Rongmei Qu, Lin Zhang, Wenhua Huang
Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR) positively correlates with TNM (tumor-node-metastasis) stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression...
May 11, 2018: International Journal of Molecular Sciences
Laurène Pfajfer, Nina K Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G Tangye, Ingrid Simonitsch-Klupp, Johannes B Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
BACKGROUND: The actin-interacting protein WDR1 promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have recently been identified in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. OBJECTIVE: Given the pleiotropic expression of WDR1, we here investigated to what extent it might control the lymphoid arm of the immune system in humans. METHODS: Histological and detailed immunological analyses were performed to elucidate the role of WDR1 in development and function of B and T lymphocytes...
May 8, 2018: Journal of Allergy and Clinical Immunology
Kotaro Tanaka, Shuichi Takeda, Kaoru Mitsuoka, Toshiro Oda, Chieko Kimura-Sakiyama, Yuichiro Maéda, Akihiro Narita
Actin depolymerizing factor (ADF) and cofilin accelerate actin dynamics by severing and disassembling actin filaments. Here, we present the 3.8 Å resolution cryo-EM structure of cofilactin (cofilin-decorated actin filament). The actin subunit structure of cofilactin (C-form) is distinct from those of F-actin (F-form) and monomeric actin (G-form). During the transition between these three conformations, the inner domain of actin (subdomains 3 and 4) and the majority of subdomain 1 move as two separate rigid bodies...
May 10, 2018: Nature Communications
Bhavani S Kowtharapu, Ruby Kala Prakasam, Radovan Murín, Dirk Koczan, Thomas Stahnke, Andreas Wree, Anselm G M Jünemann, Oliver Stachs
In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs) are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β) superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA...
May 9, 2018: International Journal of Molecular Sciences
Qasim Alhadidi, Kevin Nash, Saleh Alaqel, Muhammad Shahdaat Bin Sayeed, Zahoor A Shah
Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin-siRNA, 72-hours prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i...
May 7, 2018: Neuroscience
Valentina Zamboni, Maria Armentano, Gaia Berto, Elisa Ciraolo, Alessandra Ghigo, Donatella Garzotto, Alessandro Umbach, Ferdinando DiCunto, Elena Parmigiani, Marina Boido, Alessandro Vercelli, Nadia El-Assawy, Alessandro Mauro, Lorenzo Priano, Luisa Ponzoni, Luca Murru, Maria Passafaro, Emilio Hirsch, Giorgio R Merlo
The small-GTPase Rac1 is a key molecular regulator linking extracellular signals to actin cytoskeleton dynamics. Loss-of-function mutations in RAC1 and other genes of the Rac signaling pathway have been implicated in the pathogenesis of Intellectual Disability (ID). The Rac1 activity is negatively controlled by GAP proteins, however the effect of Rac1 hyperactivity on neuronal networking in vivo has been poorly studied. ArhGAP15 is a Rac-specific negative regulator, expressed in the main subtypes of pyramidal cortical neurons...
May 8, 2018: Scientific Reports
Jing Wu, Rui Yang, Lei Zhang, YueGuo Li, BingBing Liu, Hua Kang, ZhiJuan Fan, YaQiong Tian, ShuYe Liu, Tong Li
Deciphering the molecular networks that discriminate organ-confined breast cancer from metastatic breast cancer may lead to the identification of critical biomarkers for breast cancer invasion and aggressiveness. Here metabolomics, a global study of metabolites, has been applied to explore the metabolic alterations that characterize breast cancer progression. We profiled a total of 693 metabolites across 87 serum samples related to breast cancer (46 clinically localized and 41 metastatic breast cancer) and 49 normal samples...
May 8, 2018: Cancer Science
Zhong-Yan Zhou, Bin Huang, Shang Li, Xiao-Hui Huang, Jing-Yi Tang, Yiu Wa Kwan, Pui Man Hoi, Simon Ming-Yuen Lee
Impaired vascular integrity leads to serious cerebral vascular diseases such as intracerebral hemorrhage (ICH). In addition, high-dose statin therapy is suggested to cause increased ICH risk due to unclear effects of general inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) on the vascular system. Here we evaluated the protective effects of sodium tanshinone IIA sulfonate (STS), which has high efficacy and safety in clinical studies of ischemic stroke, by using atorvastatin (Ator) induced ICH zebrafish embryos and human umbilical vein endothelial cells (HUVECs)...
May 3, 2018: Toxicology and Applied Pharmacology
Fucheng Luo, Jessie Zhang, Kathryn Burke, Rita R Romito-DiGiacomo, Robert H Miller, Yan Yang
Myelination of the central nervous system is important for normal motor and sensory neuronal function and recent studies also link it to efficient learning and memory. Cyclin-dependent kinase 5 (Cdk5) is required for normal oligodendrocyte development, myelination and myelin repair. Here we show that conditional deletion of Cdk5 by targeting with CNP (CNP;Cdk5 CKO) results in hypomyelination and disruption of the structural integrity of Nodes of Ranvier. In addition, CNP;Cdk5 CKO mice exhibited a severe impairment of learning and memory compared to controls that may reflect perturbed neuron-glial interactions...
May 2, 2018: Experimental Neurology
Markus Schulze, Maria Hutterer, Anja Sabo, Sabine Hoja, Julia Lorenz, Tanja Rothhammer-Hampl, Christel Herold-Mende, Lucia Floßbach, Camelia Monoranu, Markus J Riemenschneider
BACKGROUND: The phosphatase chronophin (CIN/PDXP) has been shown to be an important regulator of glioma cell migration and invasion. It has two known substrates: p-Ser3-cofilin, the phosphorylated form of the actin binding protein cofilin, and pyridoxal 5'-phosphate, the active form of vitamin B6. Phosphoregulation of cofilin, among other functions, plays an important role in cell migration, whereas active vitamin B6 is a cofactor for more than one hundred enzymatic reactions. The role of CIN has yet only been examined in glioblastoma cell line models derived under serum culture conditions...
May 3, 2018: BMC Cancer
Olivier Nicole, Donald M Bell, Thierry Leste-Lasserre, Hélène Doat, François Guillemot, Emilie Pacary
Perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during neuronal development. By using in utero electroporation, we show that CaMKIIβ is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKIIβ inhibits migration, demonstrating that precise regulation of CaMKIIβ expression is required for correct neuronal migration...
April 30, 2018: Molecular Psychiatry
Vaibhav Kumar Shukla, Diva Maheshwari, Anupam Jain, Sarita Tripathi, Dinesh Kumar, Ashish Arora
BACKGROUND: Twinstar is an ADF/Cofilin family protein, which is expressed by the tsr gene in Drosophila melanogaster. Twinstar is one of the main regulators of actin cytoskeleton remodelling and is essential for vital cellular processes like cytokinesis and endocytosis. METHODS: We have characterized the structure and dynamics of Twinstar by solution NMR spectroscopy, the interaction of Twinstar with rabbit muscle actin by ITC, and biochemical activities of Twinstar through different biochemical assays using fluorescence spectroscopy and ultra-centrifugation...
April 27, 2018: Biochimica et Biophysica Acta
Bihua Bie, Jiang Wu, Joseph F Foss, Mohamed Naguib
Silent glutamatergic synapses lacking functional AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) receptors exist in several brain regions including the hippocampus. Their involvement in the dysfunction of hippocampal glutamatergic transmission in the setting of Alzheimer's disease (AD) is unknown. The present study demonstrated a decrease in the percentage of silent synapses in rats microinjected with amyloid fibrils (Aβ1-40 ) into the hippocampal CA1. Also, pairing low-frequency electric stimuli failed to induce activation of the hippocampal silent synapses in the modeled rats...
April 27, 2018: Hippocampus
Jianfeng Ge, Laurent Burnier, Maria Adamopoulou, Mei Qi Kwa, Matthias Schaks, Klemens Rottner, Cord Brakebusch
Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect...
April 26, 2018: Journal of Biological Chemistry
Sun Eun Lee, Keith P West, Robert N Cole, Kerry J Schulze, Lee S-F Wu, James D Yager, John Groopman, Parul Christian
Fetal growth restriction increases the risk of poor childhood growth and development and chronic disease in adulthood. Yet, little is known about biological pathways that mediate the long-lasting effects of suboptimal intrauterine growth. We explored the plasma proteome in a cohort of 500 Nepalese children 6-8 years of age to identify plasma proteins associated with multiple anthropometric size indicators at birth. Among 982 proteins analyzed, no proteins differed by birth weight, length, or weight-for-length indicators...
April 23, 2018: Scientific Reports
Reiko Yamagishi-Kimura, Megumi Honjo, Takashi Komizo, Takashi Ono, Akiko Yagi, Jinhee Lee, Kazunori Miyata, Tomokazu Fujimoto, Toshihiro Inoue, Hidenobu Tanihara, Junko Nishida, Takatoshi Uchida, Yuka Araki, Makoto Aihara
Purpose: To explore interactions between pilocarpine and the ROCK inhibitor, ripasudil, on IOP and pupil diameter in human eyes, and morphological and functional changes in outflow tissues in vitro. Methods: IOP and pupil diameter were measured after pilocarpine and/or ripasudil, which were topically applied in healthy subjects. Human trabecular meshwork (HTM) cells were used in a gel contraction assay, for the evaluation of phosphorylation of myosin light chain and cofilin, and immunostaining for cytoskeletal proteins...
April 1, 2018: Investigative Ophthalmology & Visual Science
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