Washington University in St. Louis Washington University Open Scholarship Arts & Sciences Electronic Theses and Dissertations Arts & Sciences Spring 5-15-2015 The Roles of MIST1 and RAB26 in yZ mogenic (Chief) Cell Differentiation and Subcellular Organization Ramon Jin Washington University in St. Louis Follow this and additional works at: https://openscholarship.wustl.edu/art_sci_etds Part of the Biology Commons Recommended Citation Jin, Ramon, "The Roles of MIST1 and RAB26 in Zymogenic (Chief) Cell Differentiation and Subcellular Organization" (2015). Arts & Sciences Electronic Theses and Dissertations. 481. https://openscholarship.wustl.edu/art_sci_etds/481 This Dissertation is brought to you for free and open access by the Arts & Sciences at Washington University Open Scholarship. It has been accepted for inclusion in Arts & Sciences Electronic Theses and Dissertations by an authorized administrator of Washington University Open Scholarship. For more information, please contact [email protected]. WASHINGTON UNIVERSITY IN ST. LOUIS Division of Biology and Biomedical Sciences Molecular Cell Biology Dissertation Examination Committee: Jason C. Mills, Chair Paul H. Taghert, Co-Chair Stuart A. Kornfeld Indira U. Mysorekar Babak Razani Joel D. Schilling The Roles of MIST1 and RAB26 in Zymogenic (Chief) Cell Differentiation and Subcellular Organization by Ramon Jin A dissertation presented to the Graduate School of Arts & Sciences of Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy May 2015 St. Louis, Missouri © 2015, Ramon Jin TABLE OF CONTENTS LIST OF FIGURES .......................................................................................................... v ACKNOWLEDGEMENTS .......................................................................................... viii ABSTRACT OF THE DISSERTATION ..................................................................... xii CHAPTER 1: Preface ....................................................................................................... 1 Introduction ..................................................................................................................... 2 Secretory Vesicle and Lysosome Trafficking ................................................................. 3 Rab Proteins as Membrane Organizers ........................................................................... 5 Developmental Regulation of Vesicle Compartments .................................................... 7 Summary ........................................................................................................................ 10 References ..................................................................................................................... 12 Figure Legends .............................................................................................................. 17 Figures ........................................................................................................................... 18 CHAPTER 2: Congenital and Acquired Diseases of the Stomach ............................. 20 Introduction ................................................................................................................... 23 Developmental/Congenital Clinical Disorders .............................................................. 23 Anatomic Development of the Stomach .................................................................... 23 Disorders .................................................................................................................... 24 Motility ................................................................................................................. 25 Cardiac Achalasia ........................................................................................... 25 Infantile Hypertrophic Pyloric Stenosis .......................................................... 26 Gastric Atresia ...................................................................................................... 27 Gastric Volvulus ................................................................................................... 28 Congenital Microgastria........................................................................................ 29 Gastric Diverticulum ............................................................................................. 30 Gastric Duplication Cysts ..................................................................................... 30 Teratomas .............................................................................................................. 31 Adult/Acquired Clinical Disorders ................................................................................ 32 Histologic Development of the Stomach ................................................................... 32 Disorders ................................................................................................................... 34 Surface Pit Cells .................................................................................................... 34 Foveolar Hyperplasia ...................................................................................... 34 Ménétrier Disease ........................................................................................... 35 Enteroendocrine Cells ........................................................................................... 36 Hypergastrinemia ............................................................................................ 37 Zollinger-Ellison Syndrome............................................................................ 38 Carcinoid Tumors ........................................................................................... 39 Parietal Cells ......................................................................................................... 41 Peptic Ulcer Disease ....................................................................................... 42 Autoimmune Gastritis/Pernicious Anemia ..................................................... 45 ii Atrophic Gastritis ............................................................................................ 47 Zymogenic (Chief) Cells....................................................................................... 48 Atrophic Gastritis/SPEM ................................................................................ 49 Intestinal Metaplasia ....................................................................................... 51 Gastric Cancer ................................................................................................. 53 Conclusions ................................................................................................................... 58 Acknowledgements ....................................................................................................... 60 References ..................................................................................................................... 61 Figure Legends .............................................................................................................. 84 Figures ........................................................................................................................... 85 CHAPTER 3: RAB26 and Rab3D are Direct Transcriptional Targets of MIST1 That Regulate Exocrine Granule Maturation ............................................ 91 Abstract .......................................................................................................................... 93 Introduction ................................................................................................................... 94 Materials and Methods .................................................................................................. 98 Results ......................................................................................................................... 109 Discussion .................................................................................................................... 116 Acknowledgements ..................................................................................................... 121 References .................................................................................................................. 122 Figure Legends ............................................................................................................ 127 Figures ......................................................................................................................... 133 CHAPTER 4: RAB26 Coordinates Lysosome Traffic and Mitochondrial Localization ................................................................................................................... 143 Summary ...................................................................................................................... 144 Introduction ................................................................................................................. 144 Results ......................................................................................................................... 146 Discussion .................................................................................................................... 155 Materials and Methods ................................................................................................ 160 Acknowledgements