The Biogenesis of Cellular Organelles

MOLECULAR BIOLOGY INTELUGENCE UNIT

Chris Mullins, Ph.D. Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland, U.S.A.

LANDES BIOSCIENCE / EUREKAH.COM KLUWER ACADEMIC / PLENUM PUBLISHERS GEORGETOWN, TEXAS NEW YORK, NEW YORK U.S.A. U.SA THE BIOGENESIS OF CELLULAR ORGANELLES

Molecular Biology Intelligence Unit

Landes Bioscience / Eurekah.com Kluwer Academic / Plenum Publishers

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ISBN: 0-306-47990-7

The Biogenesis of Cellular Organelles, edited by Chris MuUins, Landes / Kluwer dual imprint / Landes series: Molecular Biology Intelligence Unit

While the authors, editors and publisher believe that drug selection and dosage and the specifications and usage of equipment and devices, as set forth in this book, are in accord with current recommend ations and practice at the time of publication, they make no warranty, expressed or implied, with respect to material described in this book. In view of the ongoing research, equipment development, changes in governmental regulations and the rapid accumulation of information relating to the biomedical sciences, the reader is urged to carefiilly review and evaluate the information provided herein.

Library of Congress Cataloging-in-Publication Data

The biogenesis of cellular organelles / [edited by] Chris MuUins. p. ; cm. — (Molecular biology intelligence unit) Includes index. ISBN 0-306-47990-7 1. Cell organelles—Formation. I. MuUins, Chris. II. Series: Molecular biology intelligence unit (Unnumbered) [DNLM: 1. Evolution, Molecular. 2. Organelles. QH 591 B615 2004] QH581.2.B55 2004 571.6'5-dc22 2004019014 CONTENTS

Preface vii

1. Theory of Organelle Biogenesis: A Historical Perspective 1 Barbara M. Mullock and J. PaulLuzio Definitions 1 The History of Organelle Recognition 2 Protein Synthesis and Targeting 4 Organization into Complex Structures 10 Organelle Inheritance 11 Challenges 13

2. Protein Coats As Mediators of Intracellular Sorting and Organelle Biogenesis 19 Chris Mullins Clathrin: A Scaffold for Protein Coats 22 Adaptor Protein Complexes: Adaptors for Coats of the Late-Secretory and Endocytic Pathways 25 COP Complexes: Protein Coats of the Early Secretory Pathway 29 Adaptor-Related Proteins Define Novel Coats of the Secretory and Endocytic Pathways 32

3. The Role of Proteins and Lipids in Organelle Biogenesis in the Secretory Pathway 45 Thomas F. J. Martin Protein Sorting Confers a Transient Nature to Secretory Pathway Organelles AG The Molecular Machinery Regulating Compartment Identity AG General Mechanisms Employed for Cargo Exit and Entry: Fission and Fusion 50 Exit Mechanisms in Trafficking 52 Entry Mechanisms in Trafficking: Tethering, Priming and Fusion 55

4. Endoplasmic Reticulum Biogenesis: Proliferation and Differentiation 63 Erik Snapp ER Functions 65 Building Blocks of the ER 69 ER Biogenesis 73 ER Network Formation 7A ERSubdomains 80 ER Differentiation 81 Putting It All Together 84 Appendices 85 5. The Golgi Apparatus: Structure, Ftmction and Cellular Dynamics 96 Nihal Altan-Bonnet and Jennifer LippincoU-Schwartz Golgi Structure and Distribution 96 Golgi Function and Compartmentalization 99 Transport within the Golgi Complex 101 Golgi Dynamics: Interphase 102 Golgi Dynamics: Mitosis 104 Golgi As a Scaffold for Signaling Molecules 104

6. Lysosome Biogenesis and Dynamics Ill Diane McVey Ward, Shelly L. Shiflett and Jerry Kaplan Models for Lysosome Biogenesis 112 Synthesis and Delivery of Lysosomal Hydrolases 113 Synthesis and Trafficking of Lysosomal Membrane Proteins 114 Lysosomes and Endosomes Undergo Fusion and Fission 115 Lysosomes Are Capable of Fusion with the Plasma Membrane 117 Movement of Lysosomes 118

7. Nucleogenesis 127 Sui Htcang The Nuclear Envelope in Mitosis 128 Post-Mitotic Biogenesis of the Nucleolus 132

8. Mitochondrial Biogenesis 138 Danielle Leuenbergery Sean P. Curran and Carla M. Koehler Mitochondrial Dynamics 139 Mitochondrial Protein Import 142 Mitochondrial Protein Export 150 The Protein Surveillance System of the Mitochondrion 150 Metal Ion Transport 152

9. The Biogenesis and Cell Biology of Peroxisomes in Human Health and Disease 164 Stanley R. Terlecky and Paul A. Walton Biogenesis of Peroxisomal Membranes 166 Early Acting Peroxins 168 The "Preperoxisome": A Precursor Organelle to the Peroxisome? 169 Molecular Mechanisms of Peroxisomal Protein Import 170

Index 177 EDITOR

Chris Mullins, Ph.D. Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland, U.S.A. Chapter 2 CONTRIBUTORS Nihal Altan-Bonnet, Ph.D. Danielle Leuenberger, Ph.D. Cell Biology and Metabolism Branch Department of Chemistry National Institute of Child Health and Biochemistry and Human Development University of California, Los Angeles National Institutes of Health Los Angeles, California, U.S.A. Bethesda, Maryland, U.S.A. Chapter 8 Chapters Jennifer Lippincott-Schwartz, Ph.D. Sean P. Curran, Ph.D. Cell Biology and Metabolism Branch Department of Chemistry National Institute of Child Health and Biochemistry and Human Development University of California, Los Angeles National Institutes of Health Los Angeles, California, U.S.A. Bethesda, Maryland, U.S.A. Chapter 8 Chapter 5

Sui Huang, Ph.D. J. Paul Luzio, Ph.D. Department of Cell and Molecular Department of Clinical Biochemistry Biology Cambridge Institute Northwestern University Medical School for Medical Research Chicago, Illinois, U.S.A. University of Cambridge Chapter 7 Addenbrooke's Hospital Cambridge, United Kingdom Jerry Kaplan, Ph.D. Chapter 1 Department of Pathology University of Utah School of Medicine Thomas F. J. Martin, Ph.D. Salt Lake City, Utah, U.S.A. Department of Biochemistry Chapter 6 University of Wisconsin Madison, Wisconsin, U.S.A. Carla M. Koehler, Ph.D. Chapter 3 Department of Chemistry and Biochemistry Diane McVey Ward, Ph.D. University of California, Los Angeles Department of Pathology Los Angeles, California, U.S.A. University of Utah School of Medicine Chapter 8 Salt Lake City, Utah, U.S.A. Chapter 6 Barbara M. Mullock, Ph.D. Stanley R. Terlecky, Ph.D. Department of Clinical Biochemistry Department of Pharmacology Cambridge Institute Wayne State University School for Medical Research of Medicine University of Cambridge Detroit, Michigan, U.S.A. Addenbrooke's Hospital Chapter 9 Cambridge, United Kingdom Chapter 1 Paul A. Walton, Ph.D. Department of Anatomy and Cell Shelly L.Shiflett Biology Department of Pathology University of Western Ontario University of Utah School of Medicine London, Ontario, Canada Salt Lake City, Utah, U.S.A. Chapter 9 Chapter 6

Erik Snapp, Ph.D. Cell Biology and Metabolism Branch National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland, U.S.A. Chapter 4 PREFACE --

The evolution of modern cell biology tools, such as confocal imaging techniques and advanced electron microscopy methodologies, has allowed for ever improving structural and functional characterizations of the cell. Such methods complement classical genetics and biochemistry in the ongoing effort to define cellular science. This is especially apparent in the area of organelle biology. Studies dating back over 100 years to the present have revealed the elaborate collection of distinctive membrane-bound cytoplasmic subcompartments, termed organelles, within the eukaryotic cell and defined their roles in mediating numerous specialized functions in cellular physiology. Organelles play an essential role in the cell in large part through ensuring a tight regulatory and functional separation of distinct chemical reactions, such as cellular respiration, and molecular processes, such as protein degradation and DNA replication. Many organelles are common to virtually all cell types (e.g., the nucleus) while others reside only in certain differentiated cells (e.g., the lysosome-related lytic granules and melanosomes found in cytotoxic T lymphocytes and melanocytes, respectively). The unique characteristics of such heterogeneous cellular organelles are dictated by their particular bio chemical composition and complement of biomolecules. The Biogenesis of Cellular Organelles seeks to describe the cellular and molecular mechanisms mediating the biogenesis, maintenance, and func tion of key eukaryotic organelles. This work consists of an initial discussion of the evolution of organelle biogenesis theory from early studies through re cent findings, overviews of the prominent cellular machineries involved in the biogenesis and maintenance of cellular organelles, and reviews of the function and biogenesis of a number of key organelles common to nearly all eukaryotic cells, including the endoplasmic reticulum, the Golgi apparatus, the lysosome, the nucleus, the mitochondria, and the peroxisome. All chapters strive to highlight recent findings and topical issues relating to organelle biology. The primary interests of this work are the biogenesis and functional events operating in mammalian cells and in some cases the analogous events in key lower eukaryotes, such as yeast and Drosophila. The reader should note that a wealth of organelles besides those covered here have also been described, such as the all important chloroplast present in plants and other photosynthetic organisms. The general themes of each chapter are as follows: Chapter one offers a historical perspective of organelle biogenesis. This chapter recounts early discoveries that formed the foundation for the modern study of organelle biology, including the role of protein sorting in organelle maintenance and methods of organelle inheritance during cell division. In this chapter the progression from early findings to more recent discoveries in developing our current views of organelle function and biogenesis are highlighted. Chapter two presents an in depth discussion of protein coats, which in concert with additional components of the cellular machinery operate to selectively sort proteins within intracellular and endocytic trafficking pathways. In this function protein coats serve as key mediators of organelle biogenesis and maintenance. The protein coat constituents described include the adaptor protein (AP) complexes and clathrin, which operate in the late-secretory and endocytic pathways, and the COP complexes, which operate in the early secretory pathway. The recently defined adaptor-related coat proteins, the GGAs and Stoned B family members, are also reviewed. Chapter three describes the cooperative role played by lipids and proteins in maintaining organelle identity and fiinction in the face of continuous biomolecular flux between compartments and to and from the plasma membrane. The key players mediating compartment identity described include the ARF and Rab GTPases, the inositol phospholipids, and members of the SNARE protein family. Chapter four provides an extensive description of the organization, fiinction, and maintenance of the endoplasmic reticulum. The remarkably dynamic nature and morphological variability of the endoplasmic reticulum are detailed along with its numerous cellular roles, including serving as the primary site for membrane protein synthesis and entry into the secretory pathway. The contribution of proliferation and differentiation of existing membranes to the generation of endoplasmic reticulum networks are also reviewed. Chapter five reviews classical and recent findings relating to the Golgi apparatus, which functions as a site for post-translational modifications of glycoproteins and glycolipids and for the selective sorting of secretory proteins to the plasma membranes or target sites within the cell. The complex morphology of the Golgi, which allows compartmentalization of distinct Golgi functions, and the dynamics of its disassembly and reassembly during the cell cycle are highlighted. Chapter six discusses the function and biogenesis of the lysosome. The role of the lysosome, and the analogous yeast vacuole, as the primary degradative compartment in the cell and current models for the biogenesis of lysosomes and related compartments are discussed. The participation of the protein sorting machinery in lysosomal maintenance and function are described. Also, the importance of the lysosome to cellular function is illustrated through discussions of a number of mutant phenotypes resulting from perturbation of lysosomal protein sorting. Chapter seven offers a review of nuclear biogenesis, or nucleogenesis. This chapter focuses on the dynamic disassembly and reassembly of the nuclear envelope during mitotic division and the cellular machinery mediating these processes. The biogenesis of nucleoli, the nuclear structures that serve as sites for ribosome biosynthesis, is also detailed. Chapter eight reviews the function, intricate structure, and biogenesis of the mitochondria, which serves as the site of cellular respiration. The unique nature of this organelle, which has prokaryotic origins and still retains it own small genome, is described, as is its essential nature in the physiology of the cell. The mode of mitochondrial biogenesis through growth and division of pre-existing mitochondria is detailed. The pathways for mitochondrial protein import and export and ion trafficking are also reviewed. Chapter nine presents an overview of peroxisome biogenesis and function. Potential modes of formation of the peroxisome, which represent an organelle rich in metabolic enzymes and activities, are discussed along with cellular factors that contribute to its biogenesis and function. This work also details the numerous peroxisomal disorders in humans, which highlights the need to address the many unanswered questions regarding the biology of this important organelle. While the discoveries described in The Biogenesis of Cellular Organelles and elsewhere illustrate our growing understanding of the fundamental processes me diating organelle biogenesis and function, they also remind us of how much remains to be discovered. The pursuit of knowledge regarding organelle biology is essential to understanding the basic science of the cell as well as human physiology. This is clearly evident from the growing observations that associate defects in organelle function to human disease. With the continued dedication of basic and clinical scientists to addressing these important questions ensured, the future of cellular biology is sure to be one of remarkable discovery.

Chris MullinSy Ph.D. National Institutes of Health I would like to acknowledge Dr. Josephine Briggs, Dr. Juan S. Bonifacino, and Dr. Leroy M. Nyberg, Jr. for their continuing encouragement and support and the National Research Council of the National Academies of Science for their sponsorship during the early stages of this project. Special thanks are extended to Dr. Rosa Puertollano for her kind and generous advice and assistance during the completion of this book. Most of all I thank the many contributors for their valuable time, exhaustive effort, and patience in the development of this project. This work is dedicated to them and all the basic and clinical researchers who strive to un derstand the biology of the eukaryotic cell.