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.- Vesicle budding 12 Vesicle targeting ? regulation by Rab GTPases 13 Tethering complexes 13 SM proteins 14 Regulation of SNARE assembly by protein phosphorylation 15 Phosphoinositides in membrane traffic 15 Regulation of de novo membrane formation 15 1 Cellular sites of clathrin-mediated membrane budding 18 2 Formation of endocytic CCVs 19 3 Machinery for CCV formation at the cell surface 23 3.1 Role of clathrin 23 3.2 Role of AP-2 24 3.2.1 Role of AP-2 in clathrin recruitment 24 3.2.2 Role of AP-2 in cargo recruitment 26 3.3 Role of endocytic accessory proteins 27 3.3.1 Endocytic accessory proteins in clathrin recruitment, assembly, and membrane curvature 27 3.3.2 Endocytic accessory proteins in cargo recruitment 29 3.4 Interactions of endocytic accessory proteins with AP-2 3.4.1 Structure of the -ear and identification of the DPF/W consensus 32 3.4.1 Structure of the -ear and identification of the DPF/W consensus ?ear-binding motif 32 3.4.2 Identification of the FXDXF consensus ?ear-binding motif 33 3.4.3 Identification of a novel WXXF-based -ear-binding motif 33 4 Clathrin trafficking at the TGN 35 4.1 AP-1 and GGA adaptor complexes 35 4.2 Structural analysis of the -ear and GAE domain 37 4.3 Enthoprotin Clint/epsinR: identification of a novel -ear/GAE domain-binding consensus motif 38 5 Concluding remarks 39 1 Introduction 47 2 Topological considerations 48 3 Extrinsic forces affecting membrane curvature 50 3.1 Cytoskeleton 50 3.2 Adhesion to curved particles 52 3.3 Coat assembly 52 4 Intrinsic forces affecting membrane curvature 54 4.1 Transbilayer area asymmetry 54 4.1.1 Physical considerations 54 4.1.2 Inward-directed lipid translocases 56 4.1.3 Outward-directed lipid translocases 57 4.1.4 Bidirectional lipid flippases 58 4.1.5 Amphipathic peptides 58 4.1.6 Lipid remodelling enzymes 59 4.2 Transbilayer curvature asymmetry 60 4.2.1 Lipid polymorphism and membrane shape 60 4.2.2 Lipid hydrolases and lipid acyltransferases 61 4.2.3 Lysobisphosphatidic acid in multivescicular endosome formation 62 4.3 Lipid domain-induced curvature 64 5 Concluding remarks 65 1 General considerations 73 2 The GTPase cycle 74 2.1 Structural features of Rab 76 2.2 Prenylation and localization of Rab GTPases 78 3 Regulation of inter-organelle trafficking and organelle transport 79 3.1 Cargo sorting and vesicle budding 79 3.2 Regulation of membrane tethering and fusion 81 3.3 Rabs and membrane microdomains 83 3.4 Organelle transport 84 3.5 The roles of Rab GTPases in signaling pathways 85 4 Rab proteins in disease and development 86 5 Perspective 86 1 Introduction 97 2 Tethering proteins in various traffic stages 99 2.1 TRAPP 99 2.2 p115 101 2.3 Uso1p 102 2.4 The COG complex 103 2.5 The exocyst 104 2.6 EEA1 106 2.7 HOPS 108 2.8 The GARP/VFT complex 109 3 Postulated functions of the tethering proteins 110 4 Emerging common features of the tethering proteins 111 5 Regulations of the tethering proteins 113 6 Tethering proteins and sorting 113 7 Future studies 114 1 Introduction 123 2 Genetic studies indicate an essential positive function for SM proteins in vesicle transport 126 3 The structure of SM proteins 128 4 SM proteins display different binding modes to SNARE molecules 129 5 Are the data suggesting an inhibitory role for SM proteins physiologically relevant? 131 6 At what stage of the vesicle tethering-docking-fusion process do SM proteins exert their effects? 133 7 Evidence for a role of SM proteins in transport and stability of syntaxins 135 8 Protein phosphorylation regulates interactions of SM proteins with syntaxins 136 9 Non-syntaxin interaction partners of SM proteins 137 9.1 Interactions of SM proteins with transport vesicle tethering complexes 137 9.2 Interaction partners that regulate the SM protein-syntaxin association 139 9.3 The Mint proteins 141 10 Do the SM proteins share a conserved function despite the different modes of interaction with SNAREs? 142 1 Introduction 152 2 Phosphorylation and control of the exocytic machinery 154 2.1 Mammalian syntaxins 154 2.2 Yeast syntaxins 158 2.3 Arabidopsis syntaxin 159 2.4 SNAP-25 and SNAP-23 159 2.5 VAMP/Synaptobrevins 162 2.6 SM Proteins 162 2.7 Synaptotagmin 164 3 Protein phosphorylation in the endocytic pathway 165 3.1 Yeast Tlg1,2 and Vps45 165 3.2 VAMP4 166 3.3 Rabs 4 and 5 166 4 Protein phosphorylation in the early secretory pathway 167 5 Conclusions 168 1 PIs metabolism 178 2 The PI kinases: their subcellular localization and role in the secretory pathway 180 2.1 The PtdIns 3-kinases 180 2.2 The PtdIns 4-kinases 182 2.3 The PtdIns monophosphate kinases 184 3 The PI phosphatases: localization and function in the secretory pathway 186 3.1 The PI 3-phosphatases 186 3.2 The PI 4-phosphatases 188 3.3 The PI 5-phosphatases 188 4 PI metabolism and disease 189 4.1 PTEN and human cancers 189 4.2 Myotubular myopathy and Charcot-Marie-Tooth disease 190 4.3 Lowe syndrome 191 5 Conclusions 192 1 MTOCs: a brief overview 200 2 Spindle pole bodies and plasma membrane biogenesis in yeast meiosis 202 2.1 PSM initiation 203 2.2 Growth and shaping of the PSM 206 2.3 Closure of the PSM 207 3 The IMC in Apicomplexa 207 4 Centrioles, basal bodies and plasma membrane 211 5 Conclusion 211 Introduction: Regulatory processes, an emerging feature in intracellular membrane traffic....Pages 1-8 Molecular mechanisms in clathrin-mediated membrane budding....Pages 9-37 Regulating membrane curvature....Pages 39-64 Functions of Rab GTPases in organelle biogenesis....Pages 65-88 Tethering proteins in membrane traffic....Pages 89-114 The function of Sec1/Munc18 proteins – Solution of the mystery in sight?....Pages 115-143 Regulation of SNARE assembly by protein phosphorylation....Pages 145-170 Phosphoinositides and membrane traffic in health and disease....Pages 171-192 Regulation of exocytotic events by centrosome-analogous structures....Pages 193-207 The subject of this volume is the molecular mechanism of the intracellular membrane trafficking, a central eukaryotic cell biological process.