Supplemental Information Figure S1. Clc-5, Clc-4 and Clc-3
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Activity-Dependent Modulation of Neuronal Sodium Channel Expression Joshua Peter Klein Yale University
Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 5-2004 Activity-dependent modulation of neuronal sodium channel expression Joshua Peter Klein Yale University. Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Part of the Medicine and Health Sciences Commons Recommended Citation Klein, Joshua Peter, "Activity-dependent modulation of neuronal sodium channel expression" (2004). Yale Medicine Thesis Digital Library. 2198. http://elischolar.library.yale.edu/ymtdl/2198 This Open Access Dissertation is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. ACTIVITY-DEPENDENT MODULATION OF NEURONAL SODIUM CHANNEL EXPRESSION A Dissertation Presented to the Faculty of the Graduate School of Yale University in Candidacy for the Degree of Doctor of Philosophy by Joshua Peter Klein Dissertation Director: Stephen G. Waxman, M.D.,Ph.D. May, 2004 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACTiViTY-DEPENDENT MODULATION OF NEURONAL SODIUM CHANNEL EXPRESSION Joshua Peter Klein 2004 ABSTRACT Action potentials initiate via the voltage-dependent opening of plasma membrane-associated sodium channels. The number and type of sodium channels in a neuronal membrane determine the quantity of sodium current that results from a given stimulus. The expression of sodium channels in neurons is plastic, and is not only altered by injury and disease, but also by subtle changes in physiologic environment. -
CLCN5 Gene Chloride Voltage-Gated Channel 5
CLCN5 gene chloride voltage-gated channel 5 Normal Function The CLCN5 gene provides instructions for making a protein called ClC-5 that transports charged atoms (ions) across cell membranes. Specifically, ClC-5 exchanges negatively charged atoms of chlorine (chloride ions) for positively charged atoms of hydrogen ( protons or hydrogen ions). Based on this function, ClC-5 is known as a H+/Cl- exchanger. ClC-5 is found primarily in the kidneys, particularly in structures called proximal tubules. These structures help to reabsorb nutrients, water, and other materials that have been filtered from the bloodstream. The kidneys reabsorb needed materials into the blood and excrete everything else into the urine. Within proximal tubule cells, ClC-5 is embedded in specialized compartments called endosomes. Endosomes are formed at the cell surface to carry proteins and other molecules to their destinations within the cell. ClC-5 transports hydrogen ions into endosomes and chloride ions out, which helps these compartments maintain the proper acidity level (pH). Endosomal pH levels must be tightly regulated for proximal tubule cells to function properly. Health Conditions Related to Genetic Changes Dent disease About 150 mutations in the CLCN5 gene have been found to cause Dent disease 1, a chronic kidney disorder that can cause kidney failure. Most of the mutations lead to the production of an abnormally short, nonfunctional version of ClC-5 or prevent cells from producing any of this protein. A loss of ClC-5 alters the regulation of endosomal pH, which disrupts the overall function of proximal tubule cells and prevents them from reabsorbing proteins and other materials into the bloodstream. -
Entrez Symbols Name Termid Termdesc 117553 Uba3,Ube1c
Entrez Symbols Name TermID TermDesc 117553 Uba3,Ube1c ubiquitin-like modifier activating enzyme 3 GO:0016881 acid-amino acid ligase activity 299002 G2e3,RGD1310263 G2/M-phase specific E3 ubiquitin ligase GO:0016881 acid-amino acid ligase activity 303614 RGD1310067,Smurf2 SMAD specific E3 ubiquitin protein ligase 2 GO:0016881 acid-amino acid ligase activity 308669 Herc2 hect domain and RLD 2 GO:0016881 acid-amino acid ligase activity 309331 Uhrf2 ubiquitin-like with PHD and ring finger domains 2 GO:0016881 acid-amino acid ligase activity 316395 Hecw2 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 GO:0016881 acid-amino acid ligase activity 361866 Hace1 HECT domain and ankyrin repeat containing, E3 ubiquitin protein ligase 1 GO:0016881 acid-amino acid ligase activity 117029 Ccr5,Ckr5,Cmkbr5 chemokine (C-C motif) receptor 5 GO:0003779 actin binding 117538 Waspip,Wip,Wipf1 WAS/WASL interacting protein family, member 1 GO:0003779 actin binding 117557 TM30nm,Tpm3,Tpm5 tropomyosin 3, gamma GO:0003779 actin binding 24779 MGC93554,Slc4a1 solute carrier family 4 (anion exchanger), member 1 GO:0003779 actin binding 24851 Alpha-tm,Tma2,Tmsa,Tpm1 tropomyosin 1, alpha GO:0003779 actin binding 25132 Myo5b,Myr6 myosin Vb GO:0003779 actin binding 25152 Map1a,Mtap1a microtubule-associated protein 1A GO:0003779 actin binding 25230 Add3 adducin 3 (gamma) GO:0003779 actin binding 25386 AQP-2,Aqp2,MGC156502,aquaporin-2aquaporin 2 (collecting duct) GO:0003779 actin binding 25484 MYR5,Myo1e,Myr3 myosin IE GO:0003779 actin binding 25576 14-3-3e1,MGC93547,Ywhah -
Aquaporin Channels in the Heart—Physiology and Pathophysiology
International Journal of Molecular Sciences Review Aquaporin Channels in the Heart—Physiology and Pathophysiology Arie O. Verkerk 1,2,* , Elisabeth M. Lodder 2 and Ronald Wilders 1 1 Department of Medical Biology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] 2 Department of Experimental Cardiology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected]; Tel.: +31-20-5664670 Received: 29 March 2019; Accepted: 23 April 2019; Published: 25 April 2019 Abstract: Mammalian aquaporins (AQPs) are transmembrane channels expressed in a large variety of cells and tissues throughout the body. They are known as water channels, but they also facilitate the transport of small solutes, gasses, and monovalent cations. To date, 13 different AQPs, encoded by the genes AQP0–AQP12, have been identified in mammals, which regulate various important biological functions in kidney, brain, lung, digestive system, eye, and skin. Consequently, dysfunction of AQPs is involved in a wide variety of disorders. AQPs are also present in the heart, even with a specific distribution pattern in cardiomyocytes, but whether their presence is essential for proper (electro)physiological cardiac function has not intensively been studied. This review summarizes recent findings and highlights the involvement of AQPs in normal and pathological cardiac function. We conclude that AQPs are at least implicated in proper cardiac water homeostasis and energy balance as well as heart failure and arsenic cardiotoxicity. However, this review also demonstrates that many effects of cardiac AQPs, especially on excitation-contraction coupling processes, are virtually unexplored. -
Combined Pharmacological Administration of AQP1 Ion Channel
www.nature.com/scientificreports OPEN Combined pharmacological administration of AQP1 ion channel blocker AqB011 and water channel Received: 15 November 2018 Accepted: 13 August 2019 blocker Bacopaside II amplifes Published: xx xx xxxx inhibition of colon cancer cell migration Michael L. De Ieso 1, Jinxin V. Pei 1, Saeed Nourmohammadi1, Eric Smith 1,2, Pak Hin Chow1, Mohamad Kourghi1, Jennifer E. Hardingham 1,2 & Andrea J. Yool 1 Aquaporin-1 (AQP1) has been proposed as a dual water and cation channel that when upregulated in cancers enhances cell migration rates; however, the mechanism remains unknown. Previous work identifed AqB011 as an inhibitor of the gated human AQP1 cation conductance, and bacopaside II as a blocker of AQP1 water pores. In two colorectal adenocarcinoma cell lines, high levels of AQP1 transcript were confrmed in HT29, and low levels in SW480 cells, by quantitative PCR (polymerase chain reaction). Comparable diferences in membrane AQP1 protein levels were demonstrated by immunofuorescence imaging. Migration rates were quantifed using circular wound closure assays and live-cell tracking. AqB011 and bacopaside II, applied in combination, produced greater inhibitory efects on cell migration than did either agent alone. The high efcacy of AqB011 alone and in combination with bacopaside II in slowing HT29 cell motility correlated with abundant membrane localization of AQP1 protein. In SW480, neither agent alone was efective in blocking cell motility; however, combined application did cause inhibition of motility, consistent with low levels of membrane AQP1 expression. Bacopaside alone or combined with AqB011 also signifcantly impaired lamellipodial formation in both cell lines. Knockdown of AQP1 with siRNA (confrmed by quantitative PCR) reduced the efectiveness of the combined inhibitors, confrming AQP1 as a target of action. -
Hereditary Kidney Disorders
A. Stavljenić-Rukavina Hereditary kidney disorders How to Cite this article: Hereditary Kidney Disorders- eJIFCC 20/01 2009 http://www.ifcc.org 5. HEREDITARY KIDNEY DISORDERS Ana Stavljenić-Rukavina 5.1 Introduction Hereditary kidney disorders represent significant risk for the development of end stage renal desease (ESRD). Most of them are recognized in childhood, or prenataly particularly those phenotypicaly expressed as anomalies on ultrasound examination (US) during pregnancy. They represent almost 50% of all fetal malformations detected by US (1). Furthermore many of urinary tract malformations are associated with renal dysplasia which leeds to renal failure. Recent advances in molecular genetics have made a great impact on better understanding of underlying molecular mechanisms in different kidney and urinary tract disorders found in childhood or adults. Even some of clinical syndromes were not recognized earlier as genetic one. In monogenic kidney diseases gene mutations have been identified for Alport syndrome and thin basement membrane disease, autosomal dominant polycystic kidney disease, and tubular transporter disorders. There is evident progress in studies of polygenic renal disorders as glomerulopathies and diabetic nephropathy. The expanded knowledge on renal physiology and pathophysiology by analyzing the phenotypes caused by defected genes might gain to earlier diagnosis and provide new diagnostic and prognostic tool. The global increasing number of patients with ESRD urges the identification of molecular pathways involved in renal pathophysiology in order to serve as targets for either prevention or intervention. Molecular genetics nowadays possess significant tools that can be used to identify genes involved in renal disease including gene expression arrays, linkage analysis and association studies. -
The Capacity of Long-Term in Vitro Proliferation of Acute Myeloid
The Capacity of Long-Term in Vitro Proliferation of Acute Myeloid Leukemia Cells Supported Only by Exogenous Cytokines Is Associated with a Patient Subset with Adverse Outcome Annette K. Brenner, Elise Aasebø, Maria Hernandez-Valladares, Frode Selheim, Frode Berven, Ida-Sofie Grønningsæter, Sushma Bartaula-Brevik and Øystein Bruserud Supplementary Material S2 of S31 Table S1. Detailed information about the 68 AML patients included in the study. # of blasts Viability Proliferation Cytokine Viable cells Change in ID Gender Age Etiology FAB Cytogenetics Mutations CD34 Colonies (109/L) (%) 48 h (cpm) secretion (106) 5 weeks phenotype 1 M 42 de novo 241 M2 normal Flt3 pos 31.0 3848 low 0.24 7 yes 2 M 82 MF 12.4 M2 t(9;22) wt pos 81.6 74,686 low 1.43 969 yes 3 F 49 CML/relapse 149 M2 complex n.d. pos 26.2 3472 low 0.08 n.d. no 4 M 33 de novo 62.0 M2 normal wt pos 67.5 6206 low 0.08 6.5 no 5 M 71 relapse 91.0 M4 normal NPM1 pos 63.5 21,331 low 0.17 n.d. yes 6 M 83 de novo 109 M1 n.d. wt pos 19.1 8764 low 1.65 693 no 7 F 77 MDS 26.4 M1 normal wt pos 89.4 53,799 high 3.43 2746 no 8 M 46 de novo 26.9 M1 normal NPM1 n.d. n.d. 3472 low 1.56 n.d. no 9 M 68 MF 50.8 M4 normal D835 pos 69.4 1640 low 0.08 n.d. -
Effects of Aquaporin 4 and Inward Rectifier
9-Experimental Surgery Effects of aquaporin 4 and inward rectifier potassium channel 4.1 on medullospinal edema after methylprednisolone treatment to suppress acute spinal cord injury in rats1 Ye LiI, Haifeng HuII, Jingchen LiuIII, Qingsan ZhuIV, Rui GuV IAssociate Professor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Conception, design, intellectual and scientific content of the study; acquisition of data; manuscript writing; critical revision. IIAttending Doctor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Acquisition of data, manuscript writing. IIIProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Scientific content of the study, acquisition of data, manuscript writing. IVProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Acquisition of data. VProfessor, Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China. Intellectual, scientific, conception and design of the study; critical revision. Abstract Purpose: To investigate the effects of aquaporin 4 (AQP4) and inward rectifier potassium channel 4.1 (Kir4.1) on medullospinal edema after treatment with methylprednisolone (MP) to suppress acute spinal cord injury (ASCI) in rats. Methods: Sprague Dawley rats were randomly divided into control, sham, ASCI, and MP- treated ASCI groups. After the induction of ASCI, we injected 30 mg/kg MP via the tail vein at various time points. The Tarlov scoring method was applied to evaluate neurological symptoms, and the wet–dry weights method was applied to measure the water content of the spinal cord. Results: The motor function score of the ASCI group was significantly lower than that of the sham group, and the spinal water content was significantly increased. -
CTNS Molecular Genetics Profile in a Persian Nephropathic Cystinosis Population
n e f r o l o g i a 2 0 1 7;3 7(3):301–310 Revista de la Sociedad Española de Nefrología www.revistanefrologia.com Original article CTNS molecular genetics profile in a Persian nephropathic cystinosis population a b a a Farideh Ghazi , Rozita Hosseini , Mansoureh Akouchekian , Shahram Teimourian , a b c,d a,b,c,d,∗ Zohreh Ataei Kachoei , Hassan Otukesh , William A. Gahl , Babak Behnam a Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran b Department of Pediatrics, Faculty of Medicine, Ali Asghar Children Hospital, Iran University of Medical Sciences (IUMS), Tehran, Iran c Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA d NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA a r t i c l e i n f o a b s t r a c t Article history: Purpose: In this report, we document the CTNS gene mutations of 28 Iranian patients with Received 26 May 2016 nephropathic cystinosis age 1–17 years. All presented initially with severe failure to thrive, Accepted 22 November 2016 polyuria, and polydipsia. Available online 24 February 2017 Methods: Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular Keywords: analysis, which involved polymerase chain reaction (PCR) amplification to determine the Cystinosis presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing CTNS of the coding exons of CTNS. -
Supplemental Material Placed on This Supplemental Material Which Has Been Supplied by the Author(S) J Med Genet
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Med Genet Supplement Supplementary Table S1: GENE MEAN GENE NAME OMIM SYMBOL COVERAGE CAKUT CAKUT ADTKD ADTKD aHUS/TMA aHUS/TMA TUBULOPATHIES TUBULOPATHIES Glomerulopathies Glomerulopathies Polycystic kidneys / Ciliopathies Ciliopathies / kidneys Polycystic METABOLIC DISORDERS AND OTHERS OTHERS AND DISORDERS METABOLIC x x ACE angiotensin-I converting enzyme 106180 139 x ACTN4 actinin-4 604638 119 x ADAMTS13 von Willebrand cleaving protease 604134 154 x ADCY10 adenylate cyclase 10 605205 81 x x AGT angiotensinogen 106150 157 x x AGTR1 angiotensin II receptor, type 1 106165 131 x AGXT alanine-glyoxylate aminotransferase 604285 173 x AHI1 Abelson helper integration site 1 608894 100 x ALG13 asparagine-linked glycosylation 13 300776 232 x x ALG9 alpha-1,2-mannosyltransferase 606941 165 centrosome and basal body associated x ALMS1 606844 132 protein 1 x x APOA1 apolipoprotein A-1 107680 55 x APOE lipoprotein glomerulopathy 107741 77 x APOL1 apolipoprotein L-1 603743 98 x x APRT adenine phosphoribosyltransferase 102600 165 x ARHGAP24 Rho GTPase-Activation protein 24 610586 215 x ARL13B ADP-ribosylation factor-like 13B 608922 195 x x ARL6 ADP-ribosylation factor-like 6 608845 215 ATPase, H+ transporting, lysosomal V0, x ATP6V0A4 605239 90 subunit a4 ATPase, H+ transporting, lysosomal x x ATP6V1B1 192132 163 56/58, V1, subunit B1 x ATXN10 ataxin -
CTNS Gene Cystinosin, Lysosomal Cystine Transporter
CTNS gene cystinosin, lysosomal cystine transporter Normal Function The CTNS gene provides instructions for making a protein called cystinosin. This protein is located in the membrane of lysosomes, which are compartments in the cell that digest and recycle materials. Proteins digested inside lysosomes are broken down into smaller building blocks, called amino acids. The amino acids are then moved out of lysosomes by transport proteins. Cystinosin is a transport protein that specifically moves the amino acid cystine out of the lysosome. Health Conditions Related to Genetic Changes Cystinosis More than 80 different mutations that are responsible for causing cystinosis have been identified in the CTNS gene. The most common mutation is a deletion of a large part of the CTNS gene (sometimes referred to as the 57-kb deletion), resulting in the complete loss of cystinosin. This deletion is responsible for approximately 50 percent of cystinosis cases in people of European descent. Other mutations result in the production of an abnormally short protein that cannot carry out its normal transport function. Mutations that change very small regions of the CTNS gene may allow the transporter protein to retain some of its usual activity, resulting in a milder form of cystinosis. Other Names for This Gene • CTNS-LSB • CTNS_HUMAN • Cystinosis • PQLC4 Additional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of CTNS (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=1497[geneid]) Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28CTNS%5BTIAB%5D%29+O R+%28Cystinosis%5BTIAB%5D%29+AND+%28Genes%5BMH%5D%29+AND+eng lish%5Bla%5D+AND+human%5Bmh%5D+AND+%22last+3600+days%22%5Bdp% 5D) Catalog of Genes and Diseases from OMIM • CYSTINOSIN (https://omim.org/entry/606272) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=CTNS[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/1497) References • Anikster Y, Shotelersuk V, Gahl WA. -
Ubiquitination of Aquaporin-2 in the Kidney
Electrolytes & Blood Pressure 7:1-4, 2009 1 Review article 1) Ubiquitination of Aquaporin-2 in the Kidney Yu-Jung Lee, M.D. and Tae-Hwan Kwon, M.D. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attach - ment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation. Key Words : kidney tubules, collecting; ubiquitination; vasopressins; aquaporin 2 The kidneys are responsible for the regulation of body This process produces concentrated urine and is essential water and electrolyte metabolism. Thus, understanding of for regulation of body water metabolism 6) . In contrast to the underlying mechanisms for renal water transport is the well-established signaling pathways for the vaso- critical. Water permeability along the nephron has already pressin-regulated AQP2 trafficking and up-regulation of been well characterized in the mammalian kidney 1) . AQP2 expression, the underlying mechanisms for AQP2 Approximately, 180 L/day of glomerular filtrate is gen- endocytosis and intracellular degradation of AQP2 protein erated in an adult human, more than 80-90% of the glomer- are unclear. So far, two hormones (prostaglandin E2 and ular filtrate is constitutively reabsorbed by the highly water dopamine) cause AQP2 internalization independent of permeable proximal tubules and descending thin limbs of S256 dephosphorylation 7, 8) .