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Analysis of Transcription Factor FOXO in the Regulation of Stress, Aging, and Neuromuscular Tissue Homeostasis in Drosophila Melanogaster

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Analysis of Transcription Factor FOXO in the Regulation of Stress, Aging, and Neuromuscular Tissue Homeostasis in Drosophila Melanogaster Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2020 Analysis of transcription factor FOXO in the regulation of stress, aging, and neuromuscular tissue homeostasis in Drosophila melanogaster Allison Birnbaum Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Recommended Citation Birnbaum, Allison, "Analysis of transcription factor FOXO in the regulation of stress, aging, and neuromuscular tissue homeostasis in Drosophila melanogaster" (2020). Graduate Theses and Dissertations. 18098. https://lib.dr.iastate.edu/etd/18098 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Analysis of transcription factor FOXO in the regulation of stress, aging, and neuromuscular tissue homeostasis in Drosophila melanogaster by Allison Birnbaum A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Genetics and Genomics Program of Study Committee: Hua Bai, Major Professor Clark Coffman Maura McGrail Joshua Selsby Yanhai Yin The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2020 Copyright © Allison Birnbaum, 2020. All rights reserved. ii DEDICATION This work is dedicated to all those who have made this dissertation possible through their unwavering support and encouragement. I would especially like to thank my grandmother Helene, whom I wish could have been here to see me graduate. I know you would be proud. iii TABLE OF CONTENTS Page NOMENCLATURE ........................................................................................................................v ACKNOWLEDGMENTS ........................................................................................................... viii ABSTRACT ................................................................................................................................... ix GENERAL INTRODUCTION ................................................................................1 1.1 Literature Review ................................................................................................................ 3 1.2 References ......................................................................................................................... 30 AGE-DEPENDENT CHANGES IN TRANSCRIPTION FACTOR FOXO TARGETING IN FEMALE DROSOPHILA MELANOGASTER ..............................................51 2.1 Abstract .............................................................................................................................. 51 2.2 Introduction ....................................................................................................................... 52 2.3 Results ............................................................................................................................... 54 2.4 Discussion .......................................................................................................................... 60 2.5 Experimental Procedures ................................................................................................... 64 2.6 Acknowledgments ............................................................................................................. 69 2.7 Author’s Contributions Statement ..................................................................................... 69 2.8 Availability of data and materials ...................................................................................... 69 2.9 Competing Interests ........................................................................................................... 70 2.10 Figure Legends ................................................................................................................ 70 2.11 References ....................................................................................................................... 72 2.12 Figures and Tables ........................................................................................................... 76 2.13 Appendix ......................................................................................................................... 86 A PROTEOMIC ANALYSIS OF THE DROSOPHILA FOXO INTERACTOME REVEALS A DYNAMIC CHANGE IN THE FOXO INTERACTING NETWORK IN RESPONSE TO OXIDATIVE STRESS .............................................................87 3.1 Abstract .............................................................................................................................. 87 3.2 Introduction ....................................................................................................................... 88 3.3 Results ............................................................................................................................... 91 3.4 Discussion ........................................................................................................................ 101 3.5 Experimental Procedures ................................................................................................. 105 3.6 Acknowledgments ........................................................................................................... 109 3.7 Competing Interests ......................................................................................................... 110 3.8 Figure and Table Legends ............................................................................................... 110 3.9 References ....................................................................................................................... 113 3.10 Figures and Tables ......................................................................................................... 120 iv FOXO REGULATES NEUROMUSCULAR JUNCTION HOMEOSTASIS DURING DROSOPHILA AGING ..............................................................................................136 4.1 Abstract ............................................................................................................................ 136 4.2 Introduction ..................................................................................................................... 137 4.3 Results ............................................................................................................................. 139 4.4 Discussion ........................................................................................................................ 147 4.5 Experimental Procedures ................................................................................................. 153 4.6 Acknowledgments ........................................................................................................... 156 4.7 Competing Interests ......................................................................................................... 157 4.8 Figure and Table Legends ............................................................................................... 157 4.9 References ....................................................................................................................... 161 4.10 Figures and Tables ......................................................................................................... 168 GENERAL CONCLUSIONS ...............................................................................178 5.1 References ....................................................................................................................... 182 v NOMENCLATURE 4EBP 4E-binding protein Ac-Tub Acetylated α-tubulin ALS amyotrophic lateral sclerosis AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid AMPK AMP-activated protein kinase ATMK ataxia-telangiectasia mutated kinase ATP Adenosine triphosphate AVLM Abdominal ventral longitudinal muscle AZ active zone BMP bone morphogenetic protein CBP CREB binding protein ChIP Chromatin immunoprecipitation CDK Cyclin-dependent kinase CNS central nervous system CREB cAMP response element-binding protein DAF-2 insulin-like growth factor 1 (IGF-1) receptor (C. elegans) DAF-16 FOXO (C. elegans) ERK Extracellular Signal-Regulated Kinase ETC electron transport chain FOXO forkhead box subclass O GABA gamma-aminobutyric acid IIS Insulin/IGF signaling vi IL-6 Interleukin 6 JNK c-Jun-N-terminal kinase MAP microtubule-associated protein MAPK Interleukin 6 MS Mass Spectrometry MST1/CST-1 mammalian Ste20-like kinase MT microtubule mTOR mechanistic target of rapamycin NADH nicotinamide adenine dinucleotide (NAD) + hydrogen (H) NF-kB nuclear factor kappa-light-chain-enhancer of activated B cells NMDA N-methyl-D-aspartate receptor NMJ neuromuscular junction Nrf2 Nuclear factor erythroid 2-related factor 2 PI3K phosphatidylinositol 3-kinase PNS peripheral nervous system PPIN protein-protein interaction network PQ paraquat PTM post-translational modification PTEN Phosphatase and tensin homolog ROS reactive oxygen species
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