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Yue Qu, Ines Hahn, Stephen Webb, Simon P Pearce, Andreas Prokop
Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organisation and function, combining versatile Drosophila genetics with super-resolution microscopy and various functional readouts...
November 23, 2016: Molecular Biology of the Cell
Cheryl Dykstra-Aiello, Glen C Jickling, Bradley P Ander, Natasha Shroff, Xinhua Zhan, DaZhi Liu, Heather Hull, Miles Orantia, Boryana S Stamova, Frank R Sharp
BACKGROUND AND PURPOSE: Although peripheral blood mRNA and micro-RNA change after ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes after stroke. METHODS: lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from patients with ischemic stroke and matched with vascular risk factor controls...
December 2016: Stroke; a Journal of Cerebral Circulation
Vivian Tang, Zenobia C Cofer, Shuang Cui, Valerie Sapp, Kathleen M Loomes, Randolph P Matthews
OBJECTIVES: Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy affecting the bile ducts of neonates. Although BA is the leading indication for pediatric liver transplantation, the etiology remains elusive. Adducin 3 (ADD3) and X-prolyl aminopeptidase 1 (XPNPEP1) are 2 genes previously identified in genome-wide association studies as potential BA susceptibility genes. Using zebrafish, we investigated the importance of ADD3 and XPNPEP1 in functional studies. METHODS: To determine whether loss of either gene leads to biliary defects, we performed morpholino antisense oligonucleotide (MO) knockdown studies targeting add3a and xpnpep1 in zebrafish...
November 2016: Journal of Pediatric Gastroenterology and Nutrition
S Tentori, C Lanzani, L Citterio, E Brioni, M Simonini, L Zagato, E Messaggio, P Manunta
OBJECTIVE: The genetic basis of salt sensitive (SSH) hypertension consists in a very complex network of dynamic interaction among genetic-environmental factors that may change with aging. The existence of a regulatory genetic network (RGN) as triggering mechanism of SSH has been already postulated for Adducin-Endogenous Ouabain-Na+-K+ ATPase (ADD-EO-NKA) system. The observation that Klotho (KL) is a newly discovered aging suppressor gene can directly affect the Na+, K+-ATPase activity opening new possible interaction with the RGN...
September 2016: Journal of Hypertension
Taina Franco, Haiyan Chu, Philip S Low
Two major complexes form structural bridges that connect the erythrocyte membrane to its underlying spectrin-based cytoskeleton. Although the band 3-ankyrin bridge may account for most of the membrane-to-cytoskeleton interactions, the linkage between the cytoplasmic domain of band 3 (cdb3) and adducin has also been shown to be critical to membrane integrity. In the present paper, we demonstrate that adducin, a major component of the spectrin-actin junctional complex, binds primarily to residues 246-264 of cdb3, and mutation of two exposed glutamic acid residues within this sequence completely abrogates both α- and β-adducin binding...
October 1, 2016: Biochemical Journal
Hayet Soualmia, Abir Ben Romdhane, Fatma Midani, Amani Kallel, Riadh Jemaa, Moncef Feki, Naziha Kaabachi
BACKGROUND: Adducin is a membrane cytoskeletal protein, consisting of three subunits: α, β, and γ subunits encoded by three different genes (ADD1, ADD2, ADD3). A specific mutation G460T of the α-adducin gene (ADD1) is associated with high renal tubular sodium reabsorption. This mutation is associated with salt sensitivity and may influence the risk of hypertension. In this study, we investigated the relationship between the G460T polymorphism of the ADD1 and essential hypertension (EH) in the Tunisian population...
2016: Clinical Laboratory
Salim Yuce, Enver Sancakdar, Gokhan Bağcı, Sema Koc, Hande Kucuk Kurtulgan, Binnur Bağcı, Mansur Doğan, İsmail Onder Uysal
OBJECTIVE: Tinnitus is described as a disturbing sound sensation in the absence of external stimulation. We aimed to investigate whether there is any relationship between severe chronic tinnitus and angiotensin-converting enzyme (ACE) I/D and α-adducin (ADD1) G460W gene polymorphisms. MATERIALS AND METHODS: The patient group and control group consisted of 89 and 104 individuals, respectively. The evaluation of tinnitus was performed using the Strukturiertes Tinnitus-Interview (STI)...
April 2016: Journal of International Advanced Otology
Samantha Kohli, Rahul Kumar, Mohit Gupta, Sanjay Tyagi, M A Qadar Pasha
OBJECTIVE: Impairment of the renin-angiotensinogen-aldosterone system (RAAS), one of the characteristics of essential hypertension (EH), imbalances vascular homeostasis. Despite inconsistent reports on individual single nucleotide polymorphisms (SNPs) as a major predictor of EH, interactions among RAAS genetic variants are rarely investigated. METHODS: Using SNP markers, we studied potential interactions between angiotensin 1 converting enzyme (ACE), angiotensinogen (AGT), angiotensin II-type 1 receptor (AGTR1), and α adducin (ADD1) variants and their correlation with clinical endpoints in 545 individuals with hypertension and 400 age- and ethnicity-matched unrelated controls...
2016: Heart Asia
Timothy J Satchwell, Amanda J Bell, Bethan R Hawley, Stephanie Pellegrin, Kathryn E Mordue, Cees Th B M van Deursen, Nicole Heitink-Ter Braak, Gerwin Huls, Mathie P G Leers, Eline Overwater, Rienk Y J Tamminga, Bert van der Zwaag, Elisa Fermo, Paola Bianchi, Richard van Wijk, Ashley M Toye
Ankyrin-R provides a key link between band 3 and the spectrin cytoskeleton that helps to maintain the highly specialized erythrocyte biconcave shape. Ankyrin deficiency results in fragile spherocytic erythrocytes with reduced band 3 and protein 4.2 expression. We use in vitro differentiation of erythroblasts transduced with shRNAs targeting ANK1 to generate erythroblasts and reticulocytes with a novel ankyrin-R 'near null' human phenotype with less than 5% of normal ankyrin expression. Using this model, we demonstrate that absence of ankyrin negatively impacts the reticulocyte expression of a variety of proteins, including band 3, glycophorin A, spectrin, adducin and, more strikingly, protein 4...
September 2016: Haematologica
Masanori Harada, Taro Takeshima, Masanobu Okayama, Eiji Kajii
PURPOSE: To identify the differences in genotype frequencies of salt-sensitive genes between residents of fishing communities (FCs) and nonfishing communities (NFCs). METHODS: The subjects included 18,156 individuals (8,043 males [44%] and 10,113 females [56%]; average age: 57.2±16.1 years) from the general population who were registered with large-scale genome banks and resided in 30 prefectures and 78 different regions in Japan. The measurement items were age, sex, blood pressure, presence or absence of hypertension, body mass index, alcohol consumption, and smoking habit...
2016: International Journal of General Medicine
Yunzhe Lu, Toshihiko Hanada, Yuko Fujiwara, Jennifer O Nwankwo, Adam J Wieschhaus, John Hartwig, Sha Huang, Jongyoon Han, Athar H Chishti
Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin-actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin's actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate-dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO)...
July 7, 2016: Blood
Sérgio Carvalho Leite, Paula Sampaio, Vera Filipe Sousa, Joana Nogueira-Rodrigues, Rita Pinto-Costa, Luanne Laurel Peters, Pedro Brites, Mónica Mendes Sousa
The actin-binding protein adducin was recently identified as a component of the neuronal subcortical cytoskeleton. Here, we analyzed mice lacking adducin to uncover the function of this protein in actin rings. α-adducin knockout mice presented progressive axon enlargement in the spinal cord and optic and sciatic nerves, followed by axon degeneration and loss. Using stimulated emission depletion super-resolution microscopy, we show that a periodic subcortical actin cytoskeleton is assembled in every neuron type inspected including retinal ganglion cells and dorsal root ganglia neurons...
April 19, 2016: Cell Reports
Guillaume Bouyer, Luc Reininger, Ghania Ramdani, Lee D Phillips, Vikram Sharma, Stephane Egee, Gordon Langsley, Edwin Lasonder
The phosphorylation status of red blood cell proteins is strongly altered during the infection by the malaria parasite Plasmodium falciparum. We identify the key phosphorylation events that occur in the erythrocyte membrane and cytoskeleton during infection, by a comparative analysis of global phospho-proteome screens between infected (obtained at schizont stage) and uninfected RBCs. The meta-analysis of reported mass spectrometry studies revealed a novel compendium of 495 phosphorylation sites in 182 human proteins with regulatory roles in red cell morphology and stability, with about 25% of these sites specific to infected cells...
May 2016: Blood Cells, Molecules & Diseases
David S Gokhin, Velia M Fowler
PURPOSE OF REVIEW: This article discusses recent advances and unsolved questions in our understanding of actin filament organization and dynamics in the red blood cell (RBC) membrane skeleton, a two-dimensional quasi-hexagonal network consisting of (α1β1)2-spectrin tetramers interconnecting short actin filament-based junctional complexes. RECENT FINDINGS: In contrast to the long-held view that RBC actin filaments are static structures that do not exchange subunits with the cytosol, RBC actin filaments are dynamic structures that undergo subunit exchange and turnover, as evidenced by monomer incorporation experiments with rhodamine-actin and filament disruption experiments with actin-targeting drugs...
May 2016: Current Opinion in Hematology
Paolo Manunta, Mara Ferrandi, Daniele Cusi, Patrizia Ferrari, Jan Staessen, Giuseppe Bianchi
During the past 20 years, the studies on genetics or pharmacogenomics of primary hypertension provided interesting results supporting the role of genetics, but no actionable finding ready to be translated into personalized medicine. Two types of approaches have been applied: a "hypothesis-driven" approach on the candidate genes, coding for proteins involved in the biochemical machinery underlying the regulation of BP, and an "unbiased hypothesis-free" approach with GWAS, based on the randomness principles of frequentist statistics...
March 2016: Current Hypertension Reports
Charles Krieger, Simon Ji Hau Wang, Soo Hyun Yoo, Nicholas Harden
The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts...
2016: Frontiers in Cellular Neuroscience
T Gabunia, S Turabelidze-Robaqidze, R Sujashvili, I Ioramashvili, N Gogebashvili, T Sanikidze
The RBC membrane is considered as a key element in their rheology. The rheological properties of RBCs significantly depend on their membranes properties - deformability. The essential contribution of integral membrane proteins in establishing/maintaining membrane stability is due to their ability to anchor the membrane skeleton to the lipid bilayer, their capacity to bind and stabilize membrane lipids, and their ability to influence and regulate local membrane curvature. The goal of the research was investigation the alterations in RBC membrane protein component in diabetic patients with or without periodontitis...
November 2015: Georgian Medical News
Olivia Engmann, Albert Giralt, Nicolas Gervasi, Lucile Marion-Poll, Laila Gasmi, Odile Filhol, Marina R Picciotto, Diana Gilligan, Paul Greengard, Angus C Nairn, Denis Hervé, Jean-Antoine Girault
Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation...
December 7, 2015: Nature Communications
Ming-Wai Poon, James Tin Fong Zhuang, Stanley Thian Sze Wong, Stella Sun, Xiao-Qin Zhang, Gilberto Ka Kit Leung
BACKGROUND: Glioma stem cells are associated for temozolomide-resistance in glioblastoma. Adducin 3 (ADD3) is a cytoskeletal protein associated with chemoresistance but its role in glioblastoma has not been investigated. MATERIALS AND METHODS: Using an in vitro model of glioblastoma cells with acquired temozolomide resistance (D54-MG-R), the expressions of ADD3 and cancer stem cell markers were compared to those in temozolomide-sensitive glioblastoma cells (D54-MG-S)...
December 2015: Anticancer Research
J Jen, L-L Lin, H-T Chen, S-Y Liao, F-Y Lo, Y-A Tang, W-C Su, R Salgia, C-L Hsu, H-C Huang, H-F Juan, Y-C Wang
ZNF322A encoding a classical Cys2His2 zinc finger transcription factor was previously revealed as a potential oncogene in lung cancer patients. However, the oncogenic role of ZNF322A and its underlying mechanism in lung tumorigenesis remain elusive. Here we show ZNF322A protein overexpression in 123 Asian and 74 Caucasian lung cancer patients. Multivariate Cox regression analysis indicated that ZNF322A was an independent risk factor for a poor outcome in lung cancer, corroborating the Kaplan-Meier results that patients with ZNF322A protein overexpression had significantly poorer overall survival than other patients...
May 5, 2016: Oncogene
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