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https://www.readbyqxmd.com/read/28732005/filamin-actin-binding-and-titin-binding-fulfill-distinct-functions-in-z-disc-cohesion
#1
Nicanor González-Morales, Tristan K Holenka, Frieder Schöck
Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28727243/filamin-a-expression-predicts-early-recurrence-of-hepatocellular-carcinoma-after-hepatectomy
#2
Matteo Donadon, Luca Di Tommaso, Cristiana Soldani, Barbara Franceschini, Alfonso Terrone, Antonio Mimmo, Eleonora Vitali, Massimo Roncalli, Andrea Lania, Guido Torzilli
BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) after hepatectomy is very high. A predictive marker of early recurrence (ER) capable of personalizing follow-up and developing a new target therapy would be beneficial. The overexpression of Filamin-A (FLNA), a cytoskeleton protein with scaffolding properties, has recently been associated with progression in tumors. The aim of this study was to test the expression of FLNA in a cohort of patients operated for HCC. METHODS: A retrospective cohort of patients who underwent hepatic resection at Humanitas Clinical and Research Center between January 2004 and December 2014 was analyzed...
July 20, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28697756/proteomic-characterization-of-paired-non-malignant-and-malignant-african-american-prostate-epithelial-cell-lines-distinguishes-them-by-structural-proteins
#3
Jennifer S Myers, Karin A Vallega, Jason White, Kaixian Yu, Clayton C Yates, Qing-Xiang Amy Sang
BACKGROUND: While many factors may contribute to the higher prostate cancer incidence and mortality experienced by African-American men compared to their counterparts, the contribution of tumor biology is underexplored due to inadequate availability of African-American patient-derived cell lines and specimens. Here, we characterize the proteomes of non-malignant RC-77 N/E and malignant RC-77 T/E prostate epithelial cell lines previously established from prostate specimens from the same African-American patient with early stage primary prostate cancer...
July 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#4
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
July 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28666872/disruption-of-tace-filamin-interaction-can-inhibit-tace-mediated-ectodomain-shedding
#5
Yongcheol Cho, Dongeun Park, Chungho Kim
Ectodomain shedding regulates functions of many membrane proteins through the cleavage of their juxtamembrane region mainly by a disintegrin and metalloproteinase family proteinases. Tumor necrosis factor-alpha converting enzyme (TACE) is known to be responsible for phorbol myristate acetate (PMA)-induced shedding of various membrane proteins. How PMA regulates TACE-dependent shedding and how TACE exhibits substrate specificity without proteolysis of other membrane proteins are questionable. Here, we show that TACE can interact with an actin-binding protein, filamin, through 20th filamin repeat...
June 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28660794/left-main-coronary-artery-compression-by-a-dilated-main-pulmonary-artery-and-left-coronary-sinus-of-valsalva-aneurysm-in-a-patient-with-heritable-pulmonary-arterial-hypertension-and-flna-mutation
#6
Akihiro Hirashiki, Shiro Adachi, Yoshihisa Nakano, Yoshihiro Kamimura, Takeshi Ogo, Norifumi Nakanishi, Takayuki Morisaki, Hiroko Morisaki, Atsuya Shimizu, Kenji Toba, Toyoaki Murohara, Takahisa Kondo
Left main coronary artery (LMCA) disease due to external compression by a dilated main pulmonary artery (MPA) is an uncommon clinical entity. Here, we describe a 52-year-old woman with pulmonary arterial hypertension (PAH) and anteroseptal old myocardial infarction (OMI). The cause of the OMI was external compression of the LMCA by the dilated MPA and aneurysm of the left coronary sinus of Valsalva. The patient's sister (aged 56 years) had also been diagnosed with PAH and both women had a novel heterozygous splicing mutation, IVS2-2A > G (c...
June 29, 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28652603/skeletal-dysplasia-mutations-effect-on-human-filamins-structure-and-mechanosensing
#7
Jonne Seppälä, Rafael C Bernardi, Tatu J K Haataja, Maarit Hellman, Olli T Pentikäinen, Klaus Schulten, Perttu Permi, Jari Ylänne, Ulla Pentikäinen
Cells' ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28650341/two-rheumatoid-arthritis-specific-autoantigens-correlate-microbial-immunity-with-autoimmune-responses-in-joints
#8
Annalisa Pianta, Sheila L Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28638118/conformational-plasticity-and-evolutionary-analysis-of-the-myotilin-tandem-ig-domains
#9
Vid Puž, Miha Pavšič, Brigita Lenarčič, Kristina Djinović-Carugo
Myotilin is a component of the sarcomere where it plays an important role in organisation and maintenance of Z-disk integrity. This involves direct binding to F-actin and filamin C, a function mediated by its Ig domain pair. While the structures of these two individual domains are known, information about their relative orientation and flexibility remains limited. We set on to characterise the Ig domain pair of myotilin with emphasis on its molecular structure, dynamics and phylogeny. First, sequence conservation analysis of myotilin shed light on the molecular basis of myotilinopathies and revealed several motifs in Ig domains found also in I-band proteins...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595776/filamin-a-promotes-efficient-migration-and-phagocytosis-of-neutrophil-like-hl-60-cells
#10
Heike Roth, Matthias Samereier, Daniela Begandt, Robert Pick, Melanie Salvermoser, Doris Brechtefeld, Michael Schleicher, Barbara Walzog, Annette Müller-Taubenberger
The primary defense machinery to combat inflammation involves neutrophil granulocytes which in order to execute their functions rely on the efficiency of different cellular mechanisms including adhesion, spreading, migration in different environments, and phagocytosis. These functions require an accurately regulated actin network as well as the activation and adjustment of various signaling pathways. Mammalian filamins (FLNs) comprise three highly homologous large actin-binding proteins that are obvious candidates to control these processes as FLNs have been described to play a role in migration, spreading and adhesion in a variety of different cell types...
May 27, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28592659/mitochondrial-dna-3243a-g-heteroplasmy-is-associated-with-changes-in-cytoskeletal-protein-expression-and-cell-mechanics
#11
Judith Kandel, Martin Picard, Douglas C Wallace, David M Eckmann
Mitochondrial and mechanical alterations in cells have both been shown to be hallmarks of human disease. However, little research has endeavoured to establish connections between these two essential features of cells in both functional and dysfunctional situations. In this work, we hypothesized that a specific genetic alteration in mitochondrial function known to cause human disease would trigger changes in cell mechanics. Using a previously characterized set of mitochondrial cybrid cell lines, we examined the relationship between heteroplasmy for the mitochondrial DNA (mtDNA) 3243A>G mutation, the cell cytoskeleton, and resulting cellular mechanical properties...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28592633/the-phospho-caveolin-1-scaffolding-domain-dampens-force-fluctuations-in-focal-adhesions-and-promotes-cancer-cell-migration
#12
Fanrui Meng, Sandeep Saxena, Youtao Liu, Bharat Joshi, Timothy H Wong, Jay Shankar, Leonard J Foster, Pascal Bernatchez, Ivan R Nabi
Caveolin-1 (Cav1), a major Src kinase substrate phosphorylated on tyrosine-14 (Y14), contains the highly-conserved membrane-proximal caveolin scaffolding domain (CSD; amino acids 82-101). Here we show, using CSD mutants (F92A/V94A) and membrane-permeable CSD competing peptides, that Src kinase-dependent pY14Cav1 regulation of focal adhesion protein stabilization, focal adhesion tension and cancer cell migration is CSD-dependent. Quantitative proteomic analysis of Cav1-GST (1-101 amino acids) pulldowns showed 6-fold increased binding of vinculin and, to a lesser extent, α-actinin, talin and filamin, to phosphomimetic Cav1Y14D relative to non-phosphorylatable Cav1Y14F...
June 7, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#13
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28464104/postmortem-protein-degradation-is-a-key-contributor-to-fresh-pork-loin-tenderness
#14
K B Carlson, K J Prusa, C A Fedler, E M Steadham, A C Outhouse, D A King, E Huff-Lonergan, S M Lonergan
The objective of this study was to determine factors that influence tenderness independent of variation in pH, color, or marbling. To achieve the objective, 2 sample groups were chosen from a population of 159 pork loins aged 11 to 16 d. Predetermined ranges (ultimate pH, 5.54 to 5.86; marbling score, 1.0 to 3.0; percent total lipid, 1.61 to 3.37%) were defined for inclusion of individual loins in the study. The pork loins with the greatest ( = 12) and least ( = 12) Instron star probe values were assigned to 2 classification groups...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28457011/diagnosis-of-inherited-platelet-disorders-on-a-blood-smear-a-tool-to-facilitate-worldwide-diagnosis-of-platelet-disorders
#15
A Greinacher, A Pecci, S Kunishima, K Althaus, P Nurden, C L Balduini, T Bakchoul
Essentials There are many hereditary platelet disorders (HPD) but diagnosing these is challenging. We provide a method to diagnose several HPDs using standard blood smears requiring < 100 µL blood. By this approach, the underlying cause of HPD was characterized in ~25-30% of referred individuals. The method facilitates diagnosis of HPD for patients of all ages around the world. SUMMARY: Background Many hereditary thrombocytopenias and/or platelet function disorders have been identified, but diagnosis of these conditions remains challenging...
April 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28438486/pti-125-binds-and-reverses-an-altered-conformation-of-filamin-a-to-reduce-alzheimer-s-disease-pathogenesis
#16
Hoau-Yan Wang, Kuo-Chieh Lee, Zhe Pei, Amber Khan, Kalindi Bakshi, Lindsay H Burns
We show that amyloid-β1-42 (Aβ42) triggers a conformational change in the scaffolding protein filamin A (FLNA) to induce FLNA associations with α7-nicotinic acetylcholine receptor (α7nAChR) and toll-like receptor 4 (TLR4). These aberrant associations respectively enable Aβ42's toxic signaling via α7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release inflammatory cytokines. PTI-125 is a small molecule that preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR/TLR4 associations and downstream pathologies...
March 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28436273/proteome-analysis-of-sheep-b-lymphocytes-in-the-course-of-bovine-leukemia-virus-induced-leukemia
#17
Michal Reichert
Presented are the results of a study of the expression pattern of different proteins in the course of bovine leukemia virus-induced leukemia in experimental sheep and I discuss how the obtained data may be useful in gaining a better understanding of the pathogenesis of the disease, diagnosis, and for the selection of possible therapeutic targets. In cattle, the disease is characterized by life-long persistent lymphocytosis leading to leukemia/lymphoma in about 5% of infected animals. In sheep, as opposed to cattle, the course of the disease is always fatal and clinical symptoms usually occur within a three-year period after infection...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28432720/androgen-receptor-dysfunction-as-a-prevalent-manifestation-in-young-male-carriers-of-a-flna-gene-mutation
#18
Laura Carrera-García, Maximiliano Francisco Rivas-Crespo, María Soledad Fernández García
Androgenic actions require the proper signal transmission by the androgen receptor (AR), a nuclear transcription factor. This is initially located in the cell cytoplasm and should translocates to the nucleus to interact with DNA. AR functional impairment causes diverse blockage degrees of androgenic steroid action, known as androgen insensitivity syndromes. Filamin A, a protein coded by the FLNA gene, is a co-activator of various cytoplasmic factors, including AR. The mutational inactivation of the FLNA gene induces insufficiency of translocation and activation of AR...
June 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#19
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28420501/bioinformatics-analysis-of-gene-expression-profiles-in-b-cells-of-postmenopausal-osteoporosis-patients
#20
Min Ma, Shulin Luo, Wei Zhou, Liangyu Lu, Junfeng Cai, Feng Yuan, Feng Yin
OBJECTIVE: The aim of this study was to gain a better understanding of the molecular mechanisms and identify more critical genes associated with the pathogenesis of postmenopausal osteoporosis (PMOP). MATERIALS AND METHODS: Microarray data of GSE13850 were download from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified either in B cells from postmenopausal female nonsmokers with high bone mineral density (BMD) compared with those with low BMD (defined as DEG1 group) or in B cells from postmenopausal female smokers with high BMD compared with postmenopausal female nonsmokers with high BMD (defined as DEG2 group)...
April 2017: Taiwanese Journal of Obstetrics & Gynecology
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