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https://www.readbyqxmd.com/read/29382783/silac-identifies-lad1-as-a-filamin-binding-regulator-of-actin-dynamics-in-response-to-egf-and-a-marker-of-aggressive-breast-tumors
#1
Lee Roth, Swati Srivastava, Moshit Lindzen, Aldema Sas-Chen, Michal Sheffer, Mattia Lauriola, Yehoshua Enuka, Ashish Noronha, Maicol Mancini, Sara Lavi, Gabi Tarcic, Gur Pines, Nava Nevo, Ori Heyman, Tamar Ziv, Oscar M Rueda, Davide Gnocchi, Eli Pikarski, Arie Admon, Carlos Caldas, Yosef Yarden
Mutations mimicking growth factor-induced proliferation and motility characterize aggressive subtypes of mammary tumors. To unravel currently unknown players in these processes, we performed phosphoproteomic analysis on untransformed mammary epithelial cells (MCF10A) that were stimulated in culture with epidermal growth factor (EGF). We identified ladinin-1 (LAD1), a largely uncharacterized protein to date, as a phosphorylation-regulated mediator of the EGF-to-ERK pathway. Further experiments revealed that LAD1 mediated the proliferation and migration of mammary cells...
January 30, 2018: Science Signaling
https://www.readbyqxmd.com/read/29374072/asb2%C3%AE-filamin-a-axis-is-essential-for-actin-cytoskeleton-remodeling-during-heart-development
#2
Arnaud Métais, Isabelle Lamsoul, Armelle Melet, Sandrine Uttenweiler-Joseph, Renaud Poincloux, Sonia Stefanovic, Amélie Valière, Anne Gonzalez de Peredo, Alexandre Stella, Odile Burlet-Schiltz, Stephane Zaffran, Pierre G Lutz, Christel Moog-Lutz
Rationale: Heart development involves differentiation of cardiac progenitors and assembly of the contractile sarcomere apparatus of cardiomyocytes. However, little is known about the mechanisms that regulate actin cytoskeleton remodeling during cardiac cell differentiation. Objective: The Asb2α Cullin5 RING E3 ubiquitin ligase triggers polyubiquitylation and subsequent degradation by the proteasome of filamins. Here, we investigate the role of Asb2α in heart development and its mechanisms of action. Methods and Results: : Using ASB2 knockout embryos, we show that Asb2 is an essential gene, critical to heart morphogenesis and function, although its loss does not interfere with the overall patterning of the embryonic heart tube...
January 26, 2018: Circulation Research
https://www.readbyqxmd.com/read/29360750/proteomic-analysis-of-secretomes-of-oncolytic-herpes-simplex-virus-infected-squamous-cell-carcinoma-cells
#3
Shinya Tada, Masakazu Hamada, Yoshiaki Yura
Oncolytic herpes simplex virus type 1 (HSV-1) strain RH2 induced immunogenic cell death (ICD) with the release and surface exposure of damage-associated molecular patterns (DAMPs) in squamous cell carcinoma (SCC) SCCVII cells. The supernatants of RH2-infected SCCVII cells also exhibited antitumor ability by intratumoral administration in SCCVII tumor-bearing mice. The supernatants of RH2-infected cells and mock-infected cells were concentrated to produce Med24 and MedC for proteomic analyses. In Med24, the up- and down-regulated proteins were observed...
January 23, 2018: Cancers
https://www.readbyqxmd.com/read/29352010/genetics-of-syndromic-and-non-syndromic-mitral-valve-prolapse
#4
REVIEW
Thierry Le Tourneau, Jean Mérot, Antoine Rimbert, Solena Le Scouarnec, Vincent Probst, Hervé Le Marec, Robert A Levine, Jean-Jacques Schott
Mitral valve prolapse (MVP) is a common condition that affects 2%-3% of the general population. MVP is thought to include syndromic forms such as Marfan syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous degeneration and fibroelastic deficiency (FED) are regarded as two different forms of non-syndromic MVP. While FED is still considered a degenerative disease associated with ageing, frequent familial clustering has been demonstrated for myxomatous MVP. Familial and genetic studies led to the recognition of reduced penetrance and large phenotypic variability, and to the identification of prodromal or atypical forms as a part of the complex spectrum of the disease...
January 19, 2018: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/29334595/cover-image-volume-176a-number-2-february-2018
#5
Ming Hui Chen, Sangita Choudhury, Mami Hirata, Siri Khalsa, Bernard Chang, Christopher A Walsh
The cover image, by Ming Hui Chen et al., is based on the Original Article Thoracic Aortic Aneurysm in Patients with Loss of Function Filamin A Mutations: Clinical Characterization, Genetics, and Recommendations, DOI: 10.1002/ajmg.a.38580.
February 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29334594/thoracic-aortic-aneurysm-in-patients-with-loss-of-function-filamin-a-mutations-clinical-characterization-genetics-and-recommendations
#6
Ming Hui Chen, Sangita Choudhury, Mami Hirata, Siri Khalsa, Bernard Chang, Christopher A Walsh
The frequency and gender distribution of thoracic aortic aneurysm as a cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA) mutations are not known. Furthermore, there is very limited cardiovascular morbidity or mortality data in children and adults. We analyzed cardiac data on the largest series of 114 patients with LOF FLNA mutations, both children and adults, with periventricular nodular heterotopia (PVNH), including 48 study patients and 66 literature patients, median age of 22...
February 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29288417/filamin-a-flna-regulates-autophagy-of-bladder-carcinoma-cell-and-affects-its-proliferation-invasion-and-metastasis
#7
Zhenfan Wang, Chen Li, Minjun Jiang, Jianchun Chen, Min Yang, Jinxian Pu
PURPOSE: This research intended to explore the effect of FLNA on cell proliferation, invasion and migration in bladder carcinoma (BC). METHODS: Microarray analysis was performed with the TCGA data, and the results were confirmed on 20 paired BC tissues and adjacent tissues using qRT-PCR and immunohistochemistry. Transmission electron microscope (TEM) and cell fluorescence assay were used to observe the quantity of autophagosomes. The expression of autophagy-related protein (LC3-I/II, p62) was detected by western blot...
December 29, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29285101/proteomic-changes-of-cd4-cd25-forkhead-box-p3-regulatory-t-cells-in-a-30-day-rat-model-of-sepsis-survival
#8
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29284605/filamin-a-modulates-store-operated-ca2-entry-by-regulating-stim1-stromal-interaction-molecule-1-orai1-association-in-human-platelets
#9
Jose J Lopez, Letizia Albarrán, Isaac Jardín, Jose Sanchez-Collado, Pedro C Redondo, Nuria Bermejo, Regis Bobe, Tarik Smani, Juan A Rosado
OBJECTIVE: Here, we provide evidence for the role of FLNA (filamin A) in the modulation of store-operated calcium entry (SOCE). APPROACH AND RESULTS: SOCE is a major mechanism for calcium influx controlled by the intracellular Ca2+ stores. On store depletion, the endoplasmic reticulum calcium sensor STIM1 (stromal interaction molecule 1) redistributes into puncta at endoplasmic reticulum/plasma membrane junctions, a process supported by the cytoskeleton, where it interacts with the calcium channels; however, the mechanism for fine-tuning SOCE is not completely understood...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29251807/proteomic-diversity-of-high-density-lipoprotein-explains-its-association-with-clinical-outcome-in-patients-with-heart-failure
#10
Johanna Elisabeth Emmens, Donald J L Jones, Thong H Cao, Daniel C S Chan, Simon P R Romaine, Paulene A Quinn, Stefan D Anker, John G Cleland, Kenneth Dickstein, Gerasimos Filippatos, Hans L Hillege, Chim C Lang, Piotr Ponikowski, Nilesh J Samani, Dirk J van Veldhuisen, Faiz Zannad, Aeilko H Zwinderman, Marco Metra, Rudolf A de Boer, Adrian A Voors, Leong L Ng
AIMS: Previously, low high-density lipoprotein (HDL) cholesterol was found to be one of the strongest predictors of mortality and/or heart failure (HF) hospitalisation in patients with HF. We therefore performed in-depth investigation of the multifunctional HDL proteome to reveal underlying pathophysiological mechanisms explaining the association between HDL and clinical outcome. METHODS AND RESULTS: We selected a cohort of 90 HF patients with 1:1 cardiovascular death/survivor ratio from BIOSTAT-CHF...
December 18, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29240780/filamina-and-formin2-regulate-skeletal-muscular-and-intestinal-formation-through-mesenchymal-progenitor-proliferation
#11
Gewei Lian, Sneha Kanaujia, Timothy Wong, Volney Sheen
The effects of actin dependent molecular mechanisms in coordinating cellular proliferation, migration and differentiation during embryogenesis are not well-understood. We have previously shown that actin-binding Filamin A (FlnA) and actin-nucleating Formin 2 (Fmn2) influence the development of the brain causing microcephaly in mice. In this study, we broaden this phenotype to explore the effects of these two proteins in the development of extra-CNS organ systems, including the gut, muscle, and skeleton. We observed defects in rib and sternum midline closure leading to thoracoabdominal schisis in FlnA+Fmn2 knockout mice, reminiscent of the pentalogy of Cantrell syndrome...
2017: PloS One
https://www.readbyqxmd.com/read/29237676/familial-ebstein-anomaly-whole-exome-sequencing-identifies-novel-phenotype-associated-with-flna
#12
Catherine L Mercer, Gaia Andreoletti, Aisling Carroll, Anthony P Salmon, I Karen Temple, Sarah Ennis
BACKGROUND: Familial Ebstein anomaly is a rare form of congenital heart disease. We report 7 individuals among 2 generations of 1 family with Ebstein anomaly. This family was first reported in 1991 by Balaji et al in which family members were also reported to have a mild skeletal phenotype. The most likely mechanism of inheritance was concluded to be autosomal dominant. We sought to identify the genetic pathogenesis in this family using a next generation sequencing approach. METHODS AND RESULTS: Whole exome sequencing was performed in 2 cousins in this family using the Agilent SureSelect Human all Exon 51 Mb version 5 capture kit...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29234037/dynamic-regulation-of-trek1-gating-by-polycystin-2-via-a-filamin-a-mediated-cytoskeletal-mechanism
#13
Steven Li Fraine, Amanda Patel, Fabrice Duprat, Reza Sharif-Naeini
Mechanosensing is essential for several physiological functions including touch and pain sensations, osmoregulation, and controlling the myogenic tone of resistance arteries. Understanding how mechanosensitive ion channels (MSCs) are gated can provide important information regarding these processes. We have previously demonstrated that during pathological conditions such as polycystic kidney disease, polycystin 2 (TRPP2) inhibits the activity of potassium-selective MSCs through a filamin A-mediated cytoskeletal effect, and renders tubular epithelial cells susceptible to apoptosis...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29226331/a-novel-pathway-activated-by-somatostatin-receptor-type-2-sst2-inhibition-of-pituitary-tumor-cell-migration-and-invasion-through-cytoskeleton-protein-recruitment
#14
E Peverelli, E Giardino, D Treppiedi, R Catalano, F Mangili, M Locatelli, A G Lania, M Arosio, A Spada, G Mantovani
The pharmacological therapy of GH-secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of our study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA)...
December 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29212901/flnc-filamin-c-a-new-er-player-in-the-field-of-genetic-cardiomyopathies
#15
EDITORIAL
Andreas Brodehl, Anna Gaertner-Rommel, Hendrik Milting
No abstract text is available yet for this article.
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29212899/novel-mutation-in-flnc-filamin-c-causes-familial-restrictive-cardiomyopathy
#16
Nathan R Tucker, Micheal A McLellan, Dongjian Hu, Jiangchuan Ye, Victoria A Parsons, Robert W Mills, Sebastian Clauss, Elena Dolmatova, Marisa A Shea, David J Milan, Nandita S Scott, Mark Lindsay, Steven A Lubitz, Ibrahim J Domian, James R Stone, Honghuang Lin, Patrick T Ellinor
BACKGROUND: Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by impaired diastolic ventricular function resulting in a poor clinical prognosis. Rarely, heritable forms of RCM have been reported, and mutations underlying RCM have been identified in genes that govern the contractile function of the cardiomyocytes. METHODS AND RESULTS: We evaluated 8 family members across 4 generations by history, physical examination, electrocardiography, and echocardiography...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29190677/cortical-actin-nodes-their-dynamics-and-recruitment-of-podosomal-proteins-as-revealed-by-super-resolution-and-single-molecule-microscopy
#17
Yuki M Shirai, Taka A Tsunoyama, Nao Hiramoto-Yamaki, Koichiro M Hirosawa, Akihiro C E Shibata, Kenichi Kondo, Atsushi Tsurumune, Fumiyoshi Ishidate, Akihiro Kusumi, Takahiro K Fujiwara
Electron tomography of the plasma membrane (PM) identified several layers of cortical actin meshwork running parallel to the PM cytoplasmic surface throughout the PM. Here, cortical actin structures and dynamics were examined in living cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140 and ~400 nm, respectively, and single-molecule imaging. The super-resolution microscopy identified sub-micron-sized actin clusters that appeared identical by both phalloidin post-fixation staining and Lifeact-mGFP expression followed by fixation, and therefore, these actin clusters were named "actin-pl-clusters"...
2017: PloS One
https://www.readbyqxmd.com/read/29146485/in-frame-variants-in-flna-proximal-rod-1-domain-associate-with-a-predominant-cardiac-valvular-phenotype
#18
Luis Fernández, Jair Tenorio, Coral Polo-Vaquero, Elena Vallespín, María Palomares-Bralo, Sixto García-Miñaúr, Fernando Santos-Simarro, Pedro Arias, Hernán Carnicer, Silvina Giannivelli, Juan Medina, Rosa Pérez-Piaya, Jorge Solís, Mónica Rodríguez, Alexandra Villagrá, Laura Rodríguez, Julián Nevado, Víctor Martínez-Glez, Karen E Heath, Pablo Lapunzina
INTRODUCTION AND OBJECTIVES: X-linked cardiac valvular dysplasia is a rare form of male-specific congenital heart defect mainly characterized by myxomatous degeneration of the atrioventricular valves with variable hemodynamic consequences. It is caused by genetic defects in FLNA-encoded filamin A, a widely expressed actin-binding protein that regulates cytoskeleton organization. Filamin A loss of function has also been associated with often concurring neurologic and connective tissue manifestations, with mutations in the first half of the Rod 1 domain apparently expressing the full cardiac phenotype...
November 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29137275/vinculin-and-filamin-c-are-two-potential-prognostic-biomarkers-and-therapeutic-targets-for-prostate-cancer-cell-migration
#19
Jianzhong Ai, Tao Jin, Lu Yang, Qiang Wei, Yang Yang, Hong Li, Ye Zhu
Prostate cancer (PCa) is one of the most common diseases for male population, and the effective treatment for metastatic castration-resistant PCa is still lacking. To unravel the underlying mechanism of PCa cell migration, we plan to analyze the related crucial proteins and their roles. In our study, we firstly identify the differentially expressed proteins using quantitative proteomics, and confirm their mRNA expression using quantitative polymerase chain reaction (qPCR). The alterations of these proteins at DNA and mRNA levels are obtained from cBioPortal database...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29119312/when-signalling-goes-wrong-pathogenic-variants-in-structural-and-signalling-proteins-causing-cardiomyopathies
#20
Mehroz Ehsan, He Jiang, Kate L Thomson, Katja Gehmlich
Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies...
November 8, 2017: Journal of Muscle Research and Cell Motility
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