Regulatory Mechanisms of Intracellular Membrane Transport (Topics in Current Genetics)

This book deals with the molecular mechanisms of membrane trafficking, a central eukaryotic cell biological process. In the post-genomic era many essential molecules involved in intracellular membrane/protein transport are emerging. A huge task now is to compile the molecular networks that govern these processes. Understanding of regulatory processes and participating molecules are likely to reveal global cellular regulatory circuits that couple membrane trafficking with other cellular functions. Such cell biological features are only starting to emerge. This book puts special emphasis on such mechanisms and processes. The contents discusses the role of coat proteins, tethering complexes, small rab GTPases, Sec1-family proteins and SNARE molecule phosphorylation in exocytosis, endocytosis and membrane fusion. In addition, the role of lipids in vesicle formation and membrane fusion, and some specialized cell biological denovo membrane generation processes are discussed. TOC:Introduction: Regulatory Processes, an Emerging Feature in Intracellular Membrane Traffic.- Tethering Proteins in Membrane Traffic.- Molecular Mechanisms in Clathrin-Mediated Membrane Budding.- Regulation of SNARE Assembly by Protein Phosphorylation.- Functions of Rab GTPases in Organelle Biogenesis.- The Function of Sec1/Munc18 Proteins - Solution of the Mystery in Sight.- Regulating Membrane Curvature.- Regulation of Exocytotic Events by Centrosome-Analogous Structures.- Phosphoinositides and Membrane Traffic in Health and Disease.- Front......Page 1 Table of contents......Page 4 List of contributors......Page 8 Introduction: Regulatory processes, an emergingfeature in intracellular membrane traffic......Page 10 Vesicle budding......Page 12 Tethering complexes......Page 13 SM proteins......Page 14 Regulation of de novo membrane formation......Page 15 1 Cellular sites of clathrin-mediated membrane budding......Page 18 2 Formation of endocytic CCVs......Page 19 3.1 Role of clathrin......Page 23 3.2.1 Role of AP-2 in clathrin recruitment......Page 24 3.2.2 Role of AP-2 in cargo recruitment......Page 26 3.3.1 Endocytic accessory proteins in clathrin recruitment, assembly, and membrane curvature......Page 27 3.3.2 Endocytic accessory proteins in cargo recruitment......Page 29 3.4.1 Structure of the -ear and identification of the DPF/W consensus –ear-binding motif......Page 32 3.4.3 Identification of a novel WXXF-based -ear-binding motif......Page 33 4.1 AP-1 and GGA adaptor complexes......Page 35 4.2 Structural analysis of the -ear and GAE domain......Page 37 4.3 Enthoprotin (Clint/epsinR): identification of a novel -ear/GAE domain-binding consensus motif......Page 38 5 Concluding remarks......Page 39 1 Introduction......Page 47 2 Topological considerations......Page 48 3.1 Cytoskeleton......Page 50 3.3 Coat assembly......Page 52 4.1.1 Physical considerations......Page 54 4.1.2 Inward-directed lipid translocases......Page 56 4.1.3 Outward-directed lipid translocases......Page 57 4.1.5 Amphipathic peptides......Page 58 4.1.6 Lipid remodelling enzymes......Page 59 4.2.1 Lipid polymorphism and membrane shape......Page 60 4.2.2 Lipid hydrolases and lipid acyltransferases......Page 61 4.2.3 Lysobisphosphatidic acid in multivescicular endosome formation......Page 62 4.3 Lipid domain-induced curvature......Page 64 5 Concluding remarks......Page 65 1 General considerations......Page 73 2 The GTPase cycle......Page 74 2.1 Structural features of Rab......Page 76 2.2 Prenylation and localization of Rab GTPases......Page 78 3.1 Cargo sorting and vesicle budding......Page 79 3.2 Regulation of membrane tethering and fusion......Page 81 3.3 Rabs and membrane microdomains......Page 83 3.4 Organelle transport......Page 84 3.5 The roles of Rab GTPases in signaling pathways......Page 85 5 Perspective......Page 86 1 Introduction......Page 97 2.1 TRAPP......Page 99 2.2 p115......Page 101 2.3 Uso1p......Page 102 2.4 The COG complex......Page 103 2.5 The exocyst......Page 104 2.6 EEA1......Page 106 2.7 HOPS......Page 108 2.8 The GARP/VFT complex......Page 109 3 Postulated functions of the tethering proteins......Page 110 4 Emerging common features of the tethering proteins......Page 111 6 Tethering proteins and sorting......Page 113 7 Future studies......Page 114 1 Introduction......Page 123 2 Genetic studies indicate an essential positive function for SM proteins in vesicle transport......Page 126 3 The structure of SM proteins......Page 128 4 SM proteins display different binding modes to SNARE molecules......Page 129 5 Are the data suggesting an inhibitory role for SM proteins physiologically relevant?......Page 131 6 At what stage of the vesicle tethering-docking-fusion process do SM proteins exert their effects?......Page 133 7 Evidence for a role of SM proteins in transport and stability of syntaxins......Page 135 8 Protein phosphorylation regulates interactions of SM proteins with syntaxins......Page 136 9.1 Interactions of SM proteins with transport vesicle tethering complexes......Page 137 9.2 Interaction partners that regulate the SM protein-syntaxin association......Page 139 9.3 The Mint proteins......Page 141 10 Do the SM proteins share a conserved function despite the different modes of interaction with SNAREs?......Page 142 1 Introduction......Page 152 2.1 Mammalian syntaxins......Page 154 2.2 Yeast syntaxins......Page 158 2.4 SNAP-25 and SNAP-23......Page 159 2.6 SM Proteins......Page 162 2.7 Synaptotagmin......Page 164 3.1 Yeast Tlg1,2 and Vps45......Page 165 3.3 Rabs 4 and 5......Page 166 4 Protein phosphorylation in the early secretory pathway......Page 167 5 Conclusions......Page 168 1 PIs metabolism......Page 178 2.1 The PtdIns 3-kinases......Page 180 2.2 The PtdIns 4-kinases......Page 182 2.3 The PtdIns monophosphate kinases......Page 184 3.1 The PI 3-phosphatases......Page 186 3.3 The PI 5-phosphatases......Page 188 4.1 PTEN and human cancers......Page 189 4.2 Myotubular myopathy and Charcot-Marie-Tooth disease......Page 190 4.3 Lowe syndrome......Page 191 5 Conclusions......Page 192 1 MTOCs: a brief overview......Page 200 2 Spindle pole bodies and plasma membrane biogenesis in yeast meiosis......Page 202 2.1 PSM initiation......Page 203 2.2 Growth and shaping of the PSM......Page 206 3 The IMC in Apicomplexa......Page 207 5 Conclusion......Page 211 Index......Page 215 The subject of this volume is the molecular mechanism of the intracellular membrane trafficking, a central eukaryotic cell biological process.