DOCSLIB.ORG

Dopaminergic Regulation of Insulin Secretion Investigated By

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dopaminergic Regulation of Insulin Secretion Investigated By DOPAMINERGIC REGULATION OF INSULIN SECRETION INVESTIGATED BY FLUORESCENCE FLUCTUATION SPECTROSCOPY by Brittany Catherine Caldwell Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Engineering May, 2016 Nashville, Tennessee Approved by: Professor David Piston Professor Melissa Skala Professor John Gore Professor Hassane Mchaourab Professor Anne Kenworthy ACKNOWLEDGEMENTS I am very thankful to my advisor, Dave Piston, who provided me with challenging problems to solve and the methods with which to solve them. Going to the lab even on a challenging day was exciting with the lab environment Dave created. My committee members, Melissa Skala, John Gore, Hassane Mchaourab, and Anne Kenworthy provided me with excellent feedback that helped develop and strengthen my project. I am grateful for their time and patience. Working in the Piston Lab was a wonderful experience. I am thankful for all the current and previous lab members who made the lab a fun place to go each day. I owe most of my molecular biology knowledge to Alessandro Ustione who is a fantastic mentor and wonderful friend. I also want to thank Amy Elliott, Chris Reissaus, Troy Hutchens, and Zeno Lavagnino who provided helpful feedback and many laughs during my time in the Piston Lab. I am blessed with four parents who have supported me on this journey. Most importantly though, I must thank my mother who has always encouraged education, not just by words, but also by example. One of my earliest memories is dragging my children’s books over to the dining table where I watched her study so that I could be like her. Mom, without your influence, I would most certainly would not be where I am today. Thank you. Last, I want to thank my husband who has given me infinite support and encouragement on this journey. There are no words to describe how thankful I am for ii your support as we lived apart so that I could achieve my goals. This accomplishment would not have been possible without you. Thank you. iii Table of Contents LIST OF FIGURES ....................................................................................................... vii LIST OF TABLES........................................................................................................... ix Chapter 1. PHYSIOLOGY INTRODUCTION ............................................................................... 1 Introductory Comments ........................................................................................... 1 Physiology of Endocrine Pancreas .......................................................................... 2 Pancreas Physiology ........................................................................................ 2 Islets of Langerhans ......................................................................................... 3 Blood Glucose Regulation ................................................................................ 6 Diabetes Mellitus ..................................................................................................... 8 Type 1 .............................................................................................................. 8 Type 2 .............................................................................................................. 8 G Protein Coupled Receptor Regulation of Insulin ................................................ 10 Introduction ..................................................................................................... 10 G Protein-Coupled Receptor Structure ........................................................... 11 Heterotrimeric G-proteins ............................................................................... 12 GPCR in Islets (β-cell) .................................................................................... 14 Dopamine .............................................................................................................. 14 Introduction ..................................................................................................... 14 Dopamine Receptors ...................................................................................... 16 Dopamine Mediated Negative Feedback Pathway ................................................ 18 Glucose Stimulated Insulin Secretion ............................................................. 18 Dopamine in Islets .......................................................................................... 19 Proposed Dopamine Mediated Negative Feedback Pathway.......................... 21 2. FLUORESCENCE FLUCTUATION SPECTROSCOPY ........................................... 23 Tools for Understanding Protein–protein Interactions ............................................ 23 Historical Background ........................................................................................... 25 FFS Theory ........................................................................................................... 29 FCS Theory .................................................................................................... 31 PCH Theory .................................................................................................... 35 FFS Measurements ............................................................................................... 37 Instrumentation ............................................................................................... 37 Single Component Measurements .................................................................. 40 iv Two-Color Cross-Correlation Measurements .................................................. 43 Photon Counting Histogram .................................................................................. 44 Single Component PCH .................................................................................. 44 Two Component PCH ..................................................................................... 46 3. METHODOLOGY ..................................................................................................... 49 Introduction ........................................................................................................... 49 Cell Preparation .................................................................................................... 50 MIN6 Cell Line ................................................................................................ 50 Cell Media and Culturing ................................................................................ 51 Cell Transfection Background ......................................................................... 51 Cell Electroporation Transfection .................................................................... 53 Cell Imaging Buffer ......................................................................................... 54 Instrumentation and Calibration ............................................................................. 54 General Overview ........................................................................................... 54 Alignment ....................................................................................................... 56 Data Acquisition .............................................................................................. 56 Data Analysis ........................................................................................................ 58 Constructs ............................................................................................................. 61 EGFP and mApple Bacterial Expression Plasmids ......................................... 62 EGFP and mApple Mammalian Expression Plasmids ..................................... 62 EGFP DRD3 ................................................................................................... 63 EGFP DRD2 ................................................................................................... 63 mApple Gγ2 Subunit ........................................................................................ 63 mApple Linked to EGFP construct .................................................................. 64 mCerulean Gβ1 Subunit................................................................................... 65 EGFP G-protein Inwardly Rectifying Potassium Channel 3 ............................. 65 mApple G-protein Inwardly Rectifying Potassium Channel 3 .......................... 65 Protein Characterization ........................................................................................ 66 Summary ............................................................................................................... 69 4. DOPAMINE RECEPTOR SIGNALING THROUGH Gβγ COMPLEX.......................... 70 Introduction ........................................................................................................... 70 Materials and Methods .......................................................................................... 71 Constructs and Cells....................................................................................... 71 Instrumentation ............................................................................................... 72 v Theory and Data Analysis ............................................................................... 72 Two-color FFS of Separate and Linked Fluorescent Proteins ...............................
Load more

Recommended publications
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Identification of a Novel GPR143 Mutation in A
    Mao et al. BMC Ophthalmology (2021) 21:156 https://doi.org/10.1186/s12886-021-01905-7 CASE REPORT Open Access Identification of a novel GPR143 mutation in a large Chinese family with isolated foveal hypoplasia Xiying Mao†, Mingkang Chen†, Yan Yu, Qinghuai Liu, Songtao Yuan and Wen Fan* Abstract Background: Pathogenic variants of G-protein coupled receptor 143 (GPR143) gene often leads to ocular albinism type I (OA1) characterized by nystagmus, iris and fundus hypopigmentation, and foveal hypoplasia. In this study, we identified a novel hemizygous nonsense mutation in GPR143 that caused an atypical manifestation of OA1. Case presentation: We reported a large Chinese family in which all affected individuals are afflicted with poor visual acuity and foveal hypoplasia without signs of nystagmus. Fundus examination of patients showed an absent foveal reflex and mild hypopigmentation. The fourth grade of foveal hypoplasia and the reduced area of blocked fluorescence at foveal region was detected in OCT. OCTA imaging showed the absence of foveal avascular zone. In addition, the amplitude of multifocal ERG was reduced in the central ring. Gene sequencing results revealed a novel hemizygous mutation (c.939G > A) in GPR143 gene, which triggered p.W313X. However, no iris depigmentation and nystagmus were observed among both patients and carriers. Conclusions: In this study, we reported a novel nonsense mutation of GPR143 in a large family with poor visual acuity and isolated foveal hypoplasia without nystagmus, which further expanded the genetic mutation spectrum of GPR143. Keywords: GPR143 mutation, Isolated foveal hypoplasia, OA1, Case report Background as the congenital idiopathic nystagmus [3–5].
    [Show full text]
  • G Protein-Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading.
    [Show full text]
  • GPR143 Is a Prognostic Biomarker Associated with Immune in Ltration
    GPR143 is a Prognostic Biomarker Associated with Immune Inltration in Melanoma Zixuan Xing ( [email protected] ) Xi'an Jiaotong University School of Medicine Shaobo Wu Xi'an Jiaotong University Qijuan Zang Xi'an Jiaotong University School of Medicine Hao Lei Xi'an Jiaotong University Second Aliated Hospital Yi Wei Xi'an Jiaotong University Medical College First Aliated Hospital Chaonan Zhang Xi'an Jiaotong University Medical College First Aliated Hospital Bingling Dai Xi'an Jiaotong University School of Medicine Research Article Keywords: GPR143, SKCM, Immune inltration, Biomarker, TCGA, Bioinformatics Posted Date: May 4th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-430494/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/15 Abstract Background: Skin cutaneous melanoma (SKCM) is considered one of the most aggressive and lethal cancers of the skin. G-protein coupled receptor 143 (GPR143), which has been reported to cause congenital nystagmus, belongs to the superfamily of G protein- coupled receptors. Methods and Results: We analyzed the expression of GPR143 and survival of SKCM patients in SKCM via Gene Expression Proling Interactive Analysis (GEPIA). Then, logistic regression and multivariate cox analysis was used to analyze the inuence of GPR143 expression on clinicopathological elements and survival. We explored the immune response of 22 TIICs in SKCM via CIBERSORT and used TIMER to assess the correlation of GPR143 expression and immune inltration level. Finally, we used gene set enrichment analysis (GSEA) to assess the TCGA dataset. The outcomes suggest that GPR143 expression in tumor samples is remarkedly higher than in normal samples and high GPR143 expression is associated with poorer prognosis.
    [Show full text]
  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
    [Show full text]
  • Supplementary Table 1
    Supplementary Table 1. 492 genes are unique to 0 h post-heat timepoint. The name, p-value, fold change, location and family of each gene are indicated. Genes were filtered for an absolute value log2 ration 1.5 and a significance value of p ≤ 0.05. Symbol p-value Log Gene Name Location Family Ratio ABCA13 1.87E-02 3.292 ATP-binding cassette, sub-family unknown transporter A (ABC1), member 13 ABCB1 1.93E-02 −1.819 ATP-binding cassette, sub-family Plasma transporter B (MDR/TAP), member 1 Membrane ABCC3 2.83E-02 2.016 ATP-binding cassette, sub-family Plasma transporter C (CFTR/MRP), member 3 Membrane ABHD6 7.79E-03 −2.717 abhydrolase domain containing 6 Cytoplasm enzyme ACAT1 4.10E-02 3.009 acetyl-CoA acetyltransferase 1 Cytoplasm enzyme ACBD4 2.66E-03 1.722 acyl-CoA binding domain unknown other containing 4 ACSL5 1.86E-02 −2.876 acyl-CoA synthetase long-chain Cytoplasm enzyme family member 5 ADAM23 3.33E-02 −3.008 ADAM metallopeptidase domain Plasma peptidase 23 Membrane ADAM29 5.58E-03 3.463 ADAM metallopeptidase domain Plasma peptidase 29 Membrane ADAMTS17 2.67E-04 3.051 ADAM metallopeptidase with Extracellular other thrombospondin type 1 motif, 17 Space ADCYAP1R1 1.20E-02 1.848 adenylate cyclase activating Plasma G-protein polypeptide 1 (pituitary) receptor Membrane coupled type I receptor ADH6 (includes 4.02E-02 −1.845 alcohol dehydrogenase 6 (class Cytoplasm enzyme EG:130) V) AHSA2 1.54E-04 −1.6 AHA1, activator of heat shock unknown other 90kDa protein ATPase homolog 2 (yeast) AK5 3.32E-02 1.658 adenylate kinase 5 Cytoplasm kinase AK7
    [Show full text]
  • GPR143 Gene G Protein-Coupled Receptor 143
    GPR143 gene G protein-coupled receptor 143 Normal Function The GPR143 gene, also known as OA1, provides instructions for making a protein that is involved in the coloring (pigmentation) of the eyes and skin. This protein is made in the light-sensitive tissue at the back of the eye (the retina) and in skin cells. The GPR143 protein is part of a signaling pathway that controls the growth and maturation of melanosomes, which are cellular structures that produce and store a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. In the retina, this pigment also plays a critical role in normal vision. Health Conditions Related to Genetic Changes Ocular albinism More than 60 GPR143 mutations have been identified in people with the most common form of ocular albinism, which is called the Nettleship-Falls type or type 1. Most mutations alter the size or shape of the GPR143 protein. These genetic changes often prevent the abnormal protein from ever reaching melanosomes, where it is needed to control the growth of these pigment-containing structures. In other cases, the GPR143 protein reaches melanosomes normally but mutations prevent the protein from interacting with other molecules in its signaling pathway. Without functional GPR143 protein, melanosomes in skin cells and the retina can grow abnormally large. It is unclear how these giant melanosomes (macromelanosomes) are related to vision loss and other eye abnormalities in people with ocular albinism. Most forms of albinism result from a reduced amount of melanin pigment within cells. Researchers continue to study why ocular albinism occurs when cells in the retina appear to contain a substantial amount of melanin.
    [Show full text]
  • Supplementary Data, Ms Iring Et Al. Re-Revised
    Supplementary Data András Iring et al., “Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure” Supplementary Tables Supplementary Table 1. Target sequences of siRNAs used in the siRNA screen (Fig. 4A). Gene Target sequence (5´-3´) ADORA2A CGGAACAGCTCCCAGGTCT ADORA2A GCTGTTAGATCCTCCATGT ADORA2A GGCTTTCCACGGGTTCAGA ADORA2B GAGACTTCCGCTACACTTT ADORA2B GAGCTCATGGATCACTCAA ADORA2B GATGCAGCCACGAACGTGA ADRB1 CAGATCTGGTCATGGGTCT ADRB1 GTGTCATCGCCCTGGACCA ADRB1 CCATCTCGGCGCTGGTGTC ADRB2 CAAGTTCTACTTGAAGGAA ADRB2 CAACTTCTGGTGTGAGTTT ADRB2 GTCATCACAGCCATTGCCA CALCRL GATCAGTTCTGATACGCAA CALCRL GATACTCTCCGTAGTGCAT CALCRL GATTTATGATTTACCTATA CCRL1 GTATGAAGTGATCTGTATA CCRL1 GCTACTTCATCACGGCAAA CCRL1 GCATCAAACATCTGCATTT CCRL2 GACCCTACAATATTGTACT CCRL2 GCTTCTTTACCGGACTTCA CCRL2 CCTGTTGCTCTACTCCATA CELSR1 CTATGAGGAGAATCGAGTA CELSR1 GACTGAAGGTCCAGACGCA CELSR1 CCAACATCGCCACGCTGAA CELSR3 CCTTTGTAACCAGAGAGAT CELSR3 CAGCTTATGATCCAGATGT CELSR3 GCAATACCGGGAGACGCTT CXCR7 GCATGAGTGTGGATCGCTA CXCR7 GCTACGACACGCACTGCTA CXCR7 CTTTGGAGCAGAATGCCAA 2 ELTD1 CTCTTCTAATTCAACTCTT ELTD1 CAAGTTTATTACTAATGAT ELTD1 GTACCATACAGCTATAGTA FZD1 GTAACCAATGCCAAACTTT FZD1 GATTAGCCACCGAAATAAA FZD1 CAGTGTTCCGCCGAGCTCA FZD2 CGCTTTGCGCGCCTCTGGA FZD2 GACATGCAGCGCTTCCGCT FZD2 CGCACTACACGCCGCGCAT FZD4 GTATGTGCTATAATATTTA FZD4 CCATTGTCATCTTGATTAT FZD4 CCAACATGGCAGTGGAAAT FZD5 GGATTTAAGGCCCAGTTTA FZD5 GACCATAACACACTTGCTT FZD5 CAAGTGATCCTGGGAAAGA FZD6 GCATTGTATCTCTTATGTA FZD6 GTGCTTACTGAGTGTCCAA FZD6 CCAATTACTGTTCCCAGAT FZD8 CCATCTGCCTAGAGGACTA
    [Show full text]
  • Oxygenated Fatty Acids Enhance Hematopoiesis Via the Receptor GPR132
    Oxygenated Fatty Acids Enhance Hematopoiesis via the Receptor GPR132 The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Lahvic, Jamie L. 2017. Oxygenated Fatty Acids Enhance Hematopoiesis via the Receptor GPR132. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:42061504 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Oxygenated Fatty Acids Enhance Hematopoiesis via the Receptor GPR132 A dissertation presented by Jamie L. Lahvic to The Division of Medical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Developmental and Regenerative Biology Harvard University Cambridge, Massachusetts May 2017 © 2017 Jamie L. Lahvic All rights reserved. Dissertation Advisor: Leonard I. Zon Jamie L. Lahvic Oxygenated Fatty Acids Enhance Hematopoiesis via the Receptor GPR132 Abstract After their specification in early development, hematopoietic stem cells (HSCs) maintain the entire blood system throughout adulthood as well as upon transplantation. The processes of HSC specification, renewal, and homing to the niche are regulated by protein, as well as lipid signaling molecules. A screen for chemical enhancers of marrow transplant in the zebrafish identified the endogenous lipid signaling molecule 11,12-epoxyeicosatrienoic acid (11,12-EET). EET has vasodilatory properties, but had no previously described function on HSCs.
    [Show full text]
  • Doraids Final Master Thesis
    Exploring G-Protein-Coupled Receptors Regulation, Specificity and Controllability of Exosomes Release in the Neuronal Cell Line SH-SY5Y Item Type text; Electronic Thesis Authors Sadideen, Doraid Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 08/10/2021 20:16:18 Link to Item http://hdl.handle.net/10150/621166 EXPLORING G-PROTEIN-COUPLED RECEPTORS REGULATION, SPECIFICITY AND CONTROLLABILITY OF EXOSOMES RELEASE IN THE NEURONAL CELL LINE SH-SY5Y By Doraid Tarek Sadideen ____________________________ A Thesis Submitted to the Faculty of the GRADUATE INTERDISCIPLINARY PROGRAM IN PHYSIOLOGICAL SCIENCES In Partial Fulfillment of the Requirements For the Degree of MASTER OF SCIENCE In the Graduate College THE UNIVERSITY OF ARIZONA 2016 1 STATEMENT BY AUTHOR This thesis has been submitted in partial fulfillment of requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this thesis are allowable without special permission, provided that an accurate acknowledgement of the source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship.
    [Show full text]
  • Preview of “Supplement Table S4.Xls”
    Annotations for all recurrently lost regions cytoband 1p36.12 3p14.2 3q13.13 q value 0,01352 0,1513 0,085307 residual q value 0,01352 0,1513 0,085307 wide peak boundaries chr1:23457835-23714048 chr3:60396160-60637030 chr3:110456383-110657226 genes in wide peak E2F2 FHIT DPPA4 ID3 DPPA2 TCEA3 DDEFL1 TBC1D19 PI4K2B STIM2 GBA3 KCNIP4 DKFZp761B107 C4orf28 GPR125 FLJ45721 hsa-mir-218-1 CXCL3 GRSF1 HNRPD HTN1 HTN3 IBSP IGFBP7 IGJ IL8 CXCL10 KDR CXCL9 AFF1 MUC7 NKX6-1 PF4 PF4V1 PKD2 POLR2B PPEF2 PPAT PPBP PRKG2 MAPK10 PTPN13 REST CXCL6 CXCL11 CXCL5 SPINK2 SPP1 SRP72 STATH SULT1E1 UGT2B4 UGT2B7 UGT2B10 UGT2B15 UGT2B17 SPARCL1 VDP SLC4A4 HERC3 GENX-3414 CDKL2 TMPRSS11D ABCG2 ADAMTS3 CLOCK CEP135 G3BP2 HNRPDL ENAM FAM13A1 CXCL13 PAICS UGT2B11 HPSE NMU SMR3B NPFFR2 UGT2A1 CCNI hsa-mir-491 hsa-mir-31 4p15.32 4q13.1 4q13.1 (continued) 6q14.1 0,14888 0,17878 0,093693 0,14888 0,17878 0,093693 chr4:17969802-29966659 chr4:55756035-90966136 chr6:76830186-107898353 CCKAR AFM SEC31A AIM1 DHX15 AFP RUFY3 BCKDHB RBPSUH ALB WDFY3 PRDM1 SOD3 AMBN LPHN3 CCNC SLIT2 ANXA3 DKFZP564O0823 CGA SLC34A2 AREG RCHY1 CNR1 PPARGC1A ART3 ANKRD17 EPHA7 KIAA0746 BMP3 BRDG1 GABRR1 ANAPC4 BTC SMR3A GABRR2 SLA/LP CCNG2 ASAHL GRIK2 LGI2 SCARB2 COQ2 HTR1B TBC1D19 CDS1 SULT1B1 HTR1E PI4K2B CENPC1 TMPRSS11E IMPG1 STIM2 CSN1S1 MRPS18C ME1 GBA3 CSN2 COPS4 NT5E KCNIP4 CSN3 HSD17B11 PGM3 DKFZp761B107 DCK HERC5 POU3F2 C4orf28 DMP1 PLAC8 PREP GPR125 DSPP NUDT9 SIM1 FLJ45721 EPHA5 NUP54 ELOVL4 hsa-mir-218-1 EREG UGT2B28 MAP3K7 FGF5 ODAM TPBG GC HERC6 TTK GK2 SDAD1 RNGTT GNRHR UBE1L2 TBX18
    [Show full text]
  • The Ocular Albinism Type 1 (OA1) GPCR Is Ubiquitinated and Its Traffic Requires Endosomal Sorting Complex Responsible for Transp
    The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function Francesca Giordanoa,b,c,1, Sabrina Simoesa,b,c, and Graça Raposoa,b,c,2 aInstitut Curie, Centre de Recherche, Paris F-75248, France; bStructure and Membrane Compartments, Centre National de la Recherche Scientifique, UMR144, Paris F-75248, France; and cCell and Tissue Imaging Facility, Infrastructures en Biologie Sante et Agronomie, Paris F-75248, France Edited by David D. Sabatini, New York University School of Medicine, New York, NY, and approved June 7, 2011 (received for review March 2, 2011) The function of signaling receptors is tightly controlled by their tion and function remain undefined. Posttranslational modification intracellular trafficking. One major regulatory mechanism within the by ubiquitination controls intracellular trafficking events within fi endo-lysosomal system required for receptor localization and down- the endo-lysosomal system (10, 11). Ubiquitin-modi ed mem- regulation is protein modification by ubiquitination and down- brane proteins delivered from the endocytic or biosynthetic stream interactions with the endosomal sorting complex responsible pathways can be recognized by components of the endosomal sorting complex responsible for transport (ESCRT) machinery for transport (ESCRT) machinery. Whether and how these mecha- for targeting to intraluminal vesicles (ILVs) of multivesicular nisms operate to regulate endosomal sorting of mammalian G bodies (MVBs) and for subsequent
    [Show full text]