Encyclopedia of Cell Biology: Encyclopedia of Cell Biology

FrontCover......Page 1 Encyclopedia of Cell Biology......Page 4 Dedication......Page 6 Editors-in-Chief......Page 8 Volume Editors......Page 10 Section Editors......Page 12 Contributors to Volume 1......Page 18 Contents of Volume 1......Page 22 Preface......Page 26 Cell Biology: An Overview......Page 28 Basic Molecular Components and Technology......Page 32 Nucleic Acid Synthesis/Breakdown......Page 33 Protein Synthesis and Degradation......Page 34 The Laws of Thermodynamics and Living Cells......Page 36 Gibbs Free Energy Changes are Additive......Page 37 Reaction Rate and Rate Constant......Page 38 Enzyme Kinetics......Page 39 Concerted and Sequential Models......Page 40 Noncovalent Interactions Play Key Roles in Mediating Functions of Biomacromolecules......Page 41 Effect of Molecular Crowding in Living Cells......Page 42 References......Page 43 Kinetics......Page 45 Cooperativity and Allosteric Regulation......Page 48 Transition State Analogs and Catalytic Antibodies......Page 49 Hammerhead......Page 50 The Ribosome......Page 53 Relevant Website......Page 54 Glossary......Page 55 Introduction......Page 56 Physical Structure of Nucleic Acid......Page 57 Chemical Modification of Nucleic Acids......Page 58 DNA Modification by Radiation......Page 59 Nucleic Acid Sequencing......Page 60 Sanger DNA Sequencing......Page 61 Library Preparation......Page 62 Data Analysis......Page 63 Future Directions......Page 64 References......Page 65 Further Reading......Page 66 The Phosphoramidite Approach......Page 67 The H-Phosphonate Approach......Page 71 The Chemical Synthesis of Oligoribonucleotides via the Phosphoramidite Approach......Page 72 The tert-butyldimethylsilyl group......Page 73 The 1-aryl-4-alkoxypiperidin-4-yl groups......Page 74 The 2-cyanoethyloxymethyl group......Page 75 The bis-(2-acetoxyethoxy)methyl group......Page 76 Photolithography with physical or digital masks......Page 77 Electrochemical arrays......Page 78 Gene assembly from DNA microarrays......Page 80 RNA microarrays......Page 81 References......Page 83 Overview of Expression Systems......Page 85 Bacterial Expression Systems......Page 87 Cell-Free Expression Systems......Page 89 Insect Expression Systems......Page 90 Mammalian Expression Systems......Page 91 References......Page 95 Relevant Websites......Page 96 Introduction......Page 97 The Protein Source......Page 98 Accountability......Page 99 Initial Steps......Page 100 Chromatography......Page 101 Ion-Exchange Chromatography......Page 102 Metabolite affinity chromatography......Page 103 A Final Word......Page 104 Relevant Websites......Page 105 The Move to Larger Proteins......Page 106 The Role of Separations Methodology......Page 107 Challenges and Limitations......Page 108 Mass Spectrometry......Page 109 Sequence Comparisons......Page 111 References......Page 113 Phosphorylation......Page 115 Glycosylation (N- and O-linked)......Page 116 Amidation......Page 117 Carbonylation......Page 118 See also......Page 119 References......Page 120 Relevant Websites......Page 121 Protein Structure: Motifs, Folds, and Domains......Page 122 Interaction and Binding Domains......Page 123 Structural Determination by Protein Crystallography and NMR Spectroscopy......Page 124 Bioinformatic Platforms......Page 125 Domains in Evolution: Modularity and Combinatorial Protein Structure......Page 126 References......Page 127 Fundamentals of NMR Structure Determination......Page 129 Intermolecular Distance Restraints......Page 130 Orientational Restraints......Page 131 Structural Proteomics of the Bacterial Phosphotransferase System......Page 132 Basis of PRE for the Study of Sparsely Populated States......Page 134 Basis of Lifetime Line Broadening and DEST......Page 135 References......Page 136 General Principles......Page 139 Protein Folding Mechanisms and the Search for the Native State Conformation......Page 140 Misfolding......Page 142 Disordered Proteins......Page 143 Related Diseases......Page 144 References......Page 145 Introduction......Page 146 Clearance Pathways of Aggregates – Cellular UPS......Page 147 Cellular Transfer of Aggregates on Toxic Fragments......Page 148 Symptoms and Treatments of the Disease......Page 149 See also......Page 150 References......Page 151 Further Reading......Page 152 Applications......Page 153 Binding sites......Page 154 Stability......Page 155 Site-selective conjugation......Page 156 References......Page 157 Metabolic Labeling......Page 159 Affinity Labeling......Page 161 Bioorthogonal Labeling......Page 162 Chemical Biology and Drug Development......Page 163 References......Page 164 Further Reading......Page 165 Introduction......Page 166 Evolution of Drug Design......Page 167 HTS......Page 168 Drug Design and Biologics......Page 169 References......Page 170 Relevant Website......Page 171 Antibodies for In Vitro Diagnosis, in Soluble (RIA), Surface-Bound (ELISA), Cell-Bound (Fluorescence-Activated Cell.........Page 172 Design of ‘Antibody Fragments’ for Unique Clinical Applications In Vivo......Page 173 Antibody Libraries: Construction, Display, and Selection......Page 174 Maturation......Page 175 Image-Guided Surgery: From Radioactive Image-Guided Surgery (RIGS) to Fluorescence Image-Guided Surgery (FIGS)......Page 176 Relevant Websites......Page 177 Why Lipidomics?......Page 178 Description of How the Components of the Lipidome Are Usually Analyzed......Page 179 Getting Started – Sample Preparation for Lipidomic Mass Spectrometry......Page 180 Tandem mass spectrometry......Page 181 Chromatography in combination with mass spectrometry......Page 182 Tissue-imaging mass spectrometry......Page 183 Fatty acyls......Page 184 Glycerolipids......Page 185 Prenol lipids......Page 186 Lipidomics Databases and Other Online Tools......Page 187 Tissue-Imaging Mass Spectrometry......Page 188 References......Page 189 Relevant Websites......Page 190 Introduction......Page 191 Synthesis of Phosphatidic Acid......Page 192 Synthesis of Non-Amine-Containing Phospholipids......Page 193 Synthesis of Amine-Containing Phospholipids......Page 195 Synthesis of Non-Amine-Containing Phospholipids......Page 197 Roles of Phospholipids in Cell Function......Page 200 References......Page 201 Relevant Websites......Page 203 Cholesteryl Esters......Page 204 Cholesterol Biosynthesis......Page 205 Regulation of Cholesterol Biosynthesis......Page 206 Cellular Cholesterol Homeostasis......Page 207 Cholesterol in Diseases......Page 208 Steroids......Page 209 References......Page 210 Glycoglycerolipids......Page 211 Glycophosphoglycerolipids......Page 213 Glycosphingolipids......Page 214 Glycosylated sterols......Page 215 Glycosylated prenols......Page 216 Sphingolipid Backbone Biosynthesis......Page 217 Glycan Headgroup Addition......Page 220 Analysis of Glycolipids by ‘Omic’ Technologies......Page 221 Perspective on the Future of Glycolipid Research......Page 222 References......Page 223 Relevant Websites......Page 224 Lipid Classification and Nomenclature......Page 225 The Primary Mammalian Signaling Lipids......Page 226 The Complexity of Lipid Signaling......Page 227 Intracellular Signaling Lipids Interact with Proteins......Page 229 References......Page 230 Relevant Websites......Page 231 Origins......Page 232 Membrane Electrostatics......Page 233 Membrane Subdomains......Page 234 Mechanisms that Modifies the Bulk Lipid Composition of Organelles......Page 235 Membrane Curvature......Page 236 References......Page 237 Relevant Website......Page 238 Formulation of the Lipid Raft Hypothesis......Page 239 The Basis of Membrane Protein Interaction with Rafts......Page 240 Detecting Rafts in Model Membranes......Page 242 Using Detergents to Detect Rafts in Cells: Rationale and Limitations......Page 243 Detecting Rafts in Cells Using Sterol Modification......Page 244 See also......Page 245 References......Page 246 Physical–Chemical Properties of the Cell Membrane and Physiological Solutions......Page 249 Electrical Properties of the Cell and Ohm’s Law......Page 251 Determinants of the Membrane Potential......Page 252 Electrochemical Driving Force for Ion Movement......Page 253 Relative Membrane Permeability......Page 254 Do Ion Concentrations Change When the Vm Changes?......Page 256 Passive Ion Transport via Selective, Facilitated Diffusion Ion Channels......Page 257 Passive Membrane Potential Changes......Page 260 Direct Measurements of Membrane Potential and Membrane Selectivity......Page 261 Quantifying Membrane and Ion Channel Selectivity Using Voltage-Clamp......Page 262 Caveats in Measuring Physiological Vm......Page 263 Physiological Values of Vm......Page 265 References......Page 266 Relevant Websites......Page 267 Results: Protein/Enzyme Assignments of the Four Mitochondrial Compartments with an Emphasis on the Outer Mitochondrial.........Page 268 ‘Moonlighting’ Roles of the Mitochondrial Outer Membrane with Its Intracellular Neighbors......Page 269 Mitochondrial Endoplasmic Reticulum Interactions......Page 270 Cancer......Page 271 See also......Page 272 References......Page 273 Introduction......Page 275 Anatomy of a Neuron and Flow of Information......Page 276 Action Potentials......Page 277 Action Potential Propagation......Page 278 Postsynaptic Receptors/Ligand-Gated Ion Channels......Page 279 Allosteric Effectors......Page 280 References......Page 281 Protein......Page 283 CFTR and Protein Trafficking......Page 285 CFTR and Chloride Transport......Page 286 CFTR and Bicarbonate Transport......Page 288 Genetics......Page 290 Mutations affecting CFTR quantity......Page 291 Pharmacologic Approaches to Treat Patients with CF......Page 292 Relevant Websites......Page 293 Glycogen......Page 294 Starch......Page 295 Glycogen Synthesis......Page 296 Glycogen Degradation......Page 297 Starch Synthesis......Page 298 Starch Degradation......Page 299 Genetic Modification of Starch and Glycogen Metabolism......Page 300 References......Page 301 Core Protein Structure......Page 302 Cellular Functions of Proteoglycans in Health and Disease......Page 305 References......Page 308 Further Reading......Page 309 Structure and Cellular Metabolism......Page 310 Whole-Body Turnover of Hyaluronan......Page 312 Hyaluronan in Inflammatory Pathologies......Page 313 Hyaluronan in Cancer......Page 316 References......Page 317 Relevant Websites......Page 318 Glossary......Page 319 Substrates (Fuel) Availability......Page 320 Glucose transport and Its phosphorylation......Page 321 Regulation of glycogen synthesis......Page 322 Regulation of the glycolytic pathway......Page 323 Regulation of the pyruvate dehydrogenase complex......Page 324 Action of Glucagon......Page 325 Regulation of glycogen degradation......Page 326 See also......Page 327 Relevant Website......Page 328 Atomic Structures of Membrane Protein Complexes Responsible for Energization, That Is, Generation of the.........Page 329 Reaction Center of Anoxic Photosynthetic Bacteria......Page 330 Reaction Centers of Photosynthetic Plants, Algae, and Cyanobacteria......Page 331 Cytochrome b6f Complex in Oxygenic Photosynthesis Provides Electronic Connection between the Two Reaction Center Complexes......Page 332 The cytochrome b6f complex as a lipoprotein......Page 333 Pathways of proton uptake into the membrane......Page 334 The Mitochondrial Respiratory Chain......Page 335 Cytochrome bc1 Complex......Page 336 References......Page 337 Further Reading......Page 339 Glossary......Page 340 tRNA and genetic code......Page 341 Paralogous tRNA Genes/tRNA Isoacceptors......Page 344 Degenerative tRNAs in Mitochondria......Page 346 tRNA Aminoacylation......Page 347 Identify Element of tRNAs......Page 348 Proofreading of Aminoacyl-tRNAs......Page 350 tRNA in Translation......Page 351 tRNA in Translation Initiation......Page 352 tRNA in Elongation......Page 354 Surprising Number of Roles of tRNAs beyond Translation......Page 355 tRNA and GCN2 Pathway......Page 356 tRNAs for Cell Wall Synthesis......Page 357 tmRNAs......Page 358 Viral tRNA-Like Molecules......Page 359 tRNA and Human Diseases......Page 360 Mitochondrial tRNA and Human Diseases......Page 364 Therapeutics of tRNA-Related Diseases......Page 365 References......Page 366 Relevant Websites......Page 371 Shine–Dalgarno Sequence......Page 372 Cap......Page 373 AU-Rich Elements and Stem Loops in mRNA......Page 374 mRNA and Disease......Page 375 Further Reading......Page 376 Overview of Eukaryotic mRNA turnover......Page 377 Translation Elongation and mRNA Turnover......Page 378 The mRNA Cycle Hypothesis – From Polysome to p-Bodies (and Perhaps Back)......Page 379 Parting on Polysomes......Page 381 Perspectives......Page 382 References......Page 383 Introduction......Page 385 Dicer Cleaves Pre-miRNAs into miRNA–miRNA* Duplexes......Page 386 miRNAs Suppress Target mRNAs......Page 389 Alternative Biogenesis Pathways of miRNAs......Page 390 Nomenclature of miRNA......Page 391 References......Page 392 Relevant Website......Page 394 Biogenesis......Page 395 Nomenclature......Page 396 Predicting Prognosis and Response to Therapy......Page 397 miRNAs as a Target for Therapy......Page 398 IsomiRs......Page 399 LncRNAs......Page 400 References......Page 401 Relevant Websites......Page 405 From Aptamers to Riboswitches......Page 406 Ribozymes are Ubiquitous in Nature......Page 408 The glmS Ribozyme-Riboswitch......Page 411 References......Page 413 Interactions with mRNA......Page 415 Interactions with Initiation Factors......Page 416 Interactions with Initiator tRNA......Page 418 Peptide Bond Formation......Page 419 Interactions with Release Factors 1 and 2......Page 421 Interactions with Ribosome Recycling Factor......Page 423 References......Page 424 Introduction......Page 427 Functional Overview of Bacterial (C Family) and Eukaryotic (B Family) Replicative DNA Polymerases......Page 429 Sliding Clamps Are Conserved in All Cell Types......Page 431 Overview of Clamp Loader Mechanism......Page 432 Proposed Strand Exclusion Mechanism of Bacterial and Eukaryotic Replicative Helicases......Page 434 Eukaryotic Helicase Structure......Page 435 The Eukaryotic Primase......Page 436 The Primpol Primase......Page 437 The Eukaryotic RPA......Page 438 The Bacterial Replisome......Page 439 The Eukaryotic Replisome......Page 441 What Is Needed for the Future?......Page 442 References......Page 443 The End-Replication Problem......Page 449 Telomeric DNA......Page 450 Telomerase......Page 451 Telomerase Reverse Transcriptase......Page 452 Telomerase RNA......Page 453 References......Page 454 Relevant Website......Page 456 Introduction......Page 457 Proteins Associated with the Telomere......Page 458 Semiconservative Telomere Replication......Page 459 Recombination at Telomeres and ALT......Page 461 Telomeres in Cancer Cells......Page 462 Noncancer Telomere-Related Diseases......Page 463 References......Page 464 Perspective......Page 466 XPC-HR23B-CETN2......Page 467 TFIIH......Page 468 XPA-RPA......Page 469 Cockayne Syndrome......Page 470 References......Page 471 Relevant Website......Page 472 Basic Overview of the BER Pathway......Page 473 DNA Base Damage Recognition and Removal by DNA Glycosylases......Page 474 HhH DNA Glycosylases......Page 475 NEIL DNA Glycosylases......Page 476 Abasic Site Incision and Processing of DNA Strand Break Ends......Page 477 The Long-Patch BER Pathway......Page 478 Conclusions......Page 479 References......Page 480 Relevant Website......Page 481 Ligation......Page 482 Choice of DSB Repair Pathway......Page 483 NHEJ and Inhibitors......Page 484 References......Page 485 DSB Resection......Page 487 Rad51 Filament Assembly and Stability......Page 488 DNA Strand Invasion and Associated DNA Synthesis......Page 491 Synthesis-Dependent Strand Annealing......Page 492 Recombination and DNA Replication......Page 493 Recombination and Interstrand Cross-Link Repair......Page 494 Pathway Regulation and Crossover Control......Page 495 References......Page 496 Further Reading......Page 498 Core RNA Polymerase......Page 499 Bacterial RNA Polymerase Holoenzyme......Page 500 Initiation......Page 502 Elongation......Page 503 Termination......Page 505 Repression......Page 506 Activation......Page 507 Transcription and Regulation in Archaea......Page 508 References......Page 509 Further Reading......Page 511 Promoters and Transcription Factors......Page 512 Transcription Initiation and Elongation......Page 513 Chromatin......Page 514 Protein Biochemistry and Transcription In Vitro......Page 515 Some Outstanding Issues and Questions......Page 516 References......Page 517 Bacterial Enhancer Action......Page 519 Distant Promoter Activation Accompanied by DNA Looping......Page 520 Enhancer Action in Eukaryotes......Page 522 Conclusions......Page 523 References......Page 524 Relevant Websites......Page 525 The Chemistry of Splicing and the Architecture of the Intron......Page 526 The Spliceosome is Composed of snRNAs and Proteins......Page 527 Spliceosomes are Assembled from snRNPs on Introns......Page 529 The Active Site of the Spliceosome......Page 530 Alternative Splicing Creates Multiple Products from a Single Gene......Page 531 References......Page 532 Further Reading......Page 533 The Spliceosome......Page 534 Alternative Splicing......Page 536 Transcription, Chromatin Structure, and Splicing......Page 537 Diseases of the Spliceosome: Dysfunction Sheds Light on Function......Page 538 Splicing Mutations in Growth and Development......Page 539 References......Page 540 Introduction......Page 543 Temporal Regulation of Transgenes......Page 544 Homologous Recombination......Page 545 References......Page 546 Introduction......Page 548 Group I: dsDNA Viruses......Page 549 Group III: dsRNA Viruses......Page 550 Group V: (–) Strand RNA Viruses......Page 551 Group VI: (plus) Strand RNA Viruses with DNA Intermediates......Page 552 Gene Expression Strategies of RNA Viruses......Page 554 Relevant Website......Page 555 tRNA......Page 556 Ribosomes......Page 557 Cap-Dependent Protein Synthesis, the Predominant Pathway......Page 558 Other Initiation Events......Page 560 The Elongation Cycle......Page 561 Protein Synthesis Beyond the First Ribosome......Page 562 Global Regulation of Protein Synthesis......Page 563 References......Page 564 Glossary......Page 566 Nascent Polypeptides Possessing a Unique Signal Peptide Are Selectively Delivered to the ER Membrane......Page 567 The signal recognition particle (SRP) helps deliver a nascent polypeptide to the ER for co-translational translocation......Page 568 The Nascent Polypeptides Form Their Native Structures in the ER Lumen with the Help of Multiple Factors......Page 569 Glycan-Recognizing Molecular Chaperones Facilitate the Folding of Glycoproteins in the ER Lumen......Page 571 Improperly Folded Proteins Are Disposed Through the ER-Associated Degradation (ERAD) Pathway......Page 573 The Malfunctioning of Protein Folding in ER Are Known to Cause Folding Diseases......Page 574 References......Page 575 Mitochondrial Messenger RNAs......Page 576 Structural features of mitochondrial tRNAs......Page 577 Mitochondrial tRNA and aaRS in human disease......Page 578 Mitochondrial Ribosomes......Page 579 Mammalian mitochondrial system......Page 580 Polypeptide Chain Elongation......Page 581 Termination of Protein Synthesis and Ribosome Recycling in Mitochondria......Page 582 Future Directions......Page 583 Further Reading......Page 584 Relevant Websites......Page 585 The Proprotein Convertases......Page 586 General Properties......Page 587 PC1/3 Maturation in the Regulated Secretory Pathway......Page 588 Physiological Significance of PC1/3......Page 589 ProPC2 Maturation in the Regulated Secretory Pathway......Page 591 Physiological Significance of PC2......Page 592 Proprotein Convertase 5/6 (PCSK5)......Page 593 Summary and Conclusions......Page 594 References......Page 595 Glossary......Page 599 Introduction......Page 600 Identification of Protease Substrates......Page 601 Classical gel-based methods......Page 602 Gel-free methods (mass spectrometry-based)......Page 603 Negative Selection of N-termini by Combined Fractional Diagonal Chromatography (COFRADIC)......Page 605 Negative selection of N-terminal peptides by Terminal Amine Isotopic Labeling of Substrates (TAILS)......Page 606 Proteomic identification of protease cleavage site specificity......Page 607 Validation of Degradomic Data......Page 608 References......Page 610 Relevant Website......Page 612 Ubiquitin......Page 613 Ubiquitin-Conjugation System......Page 615 SUMO Family Members......Page 617 ISG15......Page 618 The 20S Core Particle: Structure and Catalytic Mechanism......Page 619 The 19S RPs: Structure and Function......Page 620 Assembly of the Proteasome......Page 621 The Proteasome......Page 622 References......Page 623 Further Reading......Page 626 Introduction......Page 627 Targeting and Entering the ER: The Beginning of a Perilous Journey......Page 628 The N-Glycosylation Quality Control Pathway......Page 630 ER Exit: The Continuation of a Productive Journey......Page 632 Location, location, location......Page 633 The fatty and sweet sides of destruction......Page 634 Getting Back Out: The Retro-Translocation of Misfolded Substrates......Page 635 At the End, the Proteasome......Page 636 References......Page 637 Introduction......Page 643 Cathepsins......Page 644 Cathepsins in the Immune Response......Page 645 Lipases......Page 646 Lysosomal Biogenesis and Its Regulation......Page 647 Endocytosis......Page 648 References......Page 649 Structure......Page 652 Substrate Profiles: Biological and Biomedical Implications......Page 653 ECM......Page 655 Transcriptional......Page 656 Natural Inhibitors......Page 657 Future Directions......Page 658 References......Page 659 Relevant Websites......Page 660 Introduction, Defining Characteristics and Phylogeny of A Disintegrin-Like and Metalloprotease Domain with Thrombospondin.........Page 661 Domain Organization and 3-Dimensional Structure......Page 663 ADAMTS13, vWF and Thrombotic Thrombocytopenic Purpura......Page 664 ADAMTS10, Tissue Microfibrils and Weill–Marchesani Syndrome......Page 665 ADAMTS Proteolysis of Versican as a Crucial Requirement for Normal Embryogenesis and Neural Function......Page 666 References......Page 667 Relevant Websites......Page 669 ADAM17, the TNFα Convertase......Page 670 ADAM17 is Crucial for EGFR Signaling......Page 671 ADAM17-Dependent EGFR Activation Protects the Skin and Intestinal Barrier......Page 672 ADAM17/TNFα and ADAM17/EGFR Signaling are Controlled by Upstream Regulators Called iRhoms......Page 673 ADAM10, A Crucial Regulator of Notch Signaling......Page 674 Other Substrates of ADAM10 and ADAM17......Page 675 Summary......Page 677 References......Page 679 Stem Region Accessory Domains......Page 681 The GPI-Anchored Serine Proteases......Page 682 The HAT/DESC Subfamily......Page 685 The Hepsin/TMPRSS Subfamily......Page 686 The Corin Subfamily......Page 687 References......Page 688 Amyloid Production......Page 692 Knockout Mice......Page 693 Prospects for Therapeutics......Page 694 Other Substrates......Page 695 Toward Structure Elucidation......Page 696 Prospects for Therapeutics......Page 697 References......Page 698 Relevant Websites......Page 700 Structure of Conventional Calpains......Page 701 The Smaller Regulatory Subunit, CAPNS1/30K......Page 702 Ca2plus: The Main Calpain Activator......Page 703 Relationship between Calpain and Caspases......Page 704 Central Nervous System......Page 705 Calpains in the Gastrointestinal Tract......Page 707 References......Page 708 Historical Background......Page 712 Cell-specific processing and trafficking......Page 713 Substrates......Page 714 Roles in immune responses......Page 715 Roles in gastric development and cancer......Page 716 Diagnostic and prognostic values in breast cancer......Page 717 Acknowledgments......Page 718 References......Page 719 Relevant Website......Page 721 Inhibition of Meprin Metalloproteases......Page 722 Meprin in Inflammation......Page 725 Meprin in Skin and Fibrosis......Page 726 References......Page 727 Tissue KLK......Page 730 Kallikrein-Related Peptidases......Page 731 See also......Page 733 References......Page 734 Further Reading......Page 735 Cystatins/Stefins......Page 737 Inhibitors of Apoptosis......Page 738 Regulation of inflammation and immunity......Page 739 Serpins......Page 740 Cysteine proteases......Page 741 Mechanism of Inhibition of MMPs......Page 742 Disease Aspects......Page 743 Relevant Website......Page 744 Platelet Production......Page 745 Platelet Structure and Function in Primary Hemostasis......Page 746 Propagation Phase......Page 747 Defects in platelet function......Page 748 Deep vein thrombosis – Overview......Page 749 Aging......Page 750 References......Page 751 Classical Pathway......Page 754 Lectin Pathway......Page 757 The Alternative Pathway......Page 759 References......Page 760 Relevant Websites......Page 762 Role of the Oral Cavity in Proteolysis......Page 763 Role of the Stomach in Proteolysis......Page 764 Role of the Small Intestine in Proteolysis......Page 765 Role of the Large Intestine in Proteolysis......Page 766 References......Page 767 Relevant Websites......Page 768 Glossary......Page 769 Inhibitors of Retroviral Proteases......Page 770 First generation of HIV-1 PR Inhibitors Approved as AIDS Drugs......Page 772 Emergence of Resistance to Clinical Inhibitors of HIV-1 PR......Page 773 Roads Not Taken – Inhibitors of HIV-1 PR That Did Not Become Drugs......Page 774 See also......Page 775 Relavant Website......Page 776 Overview of the system......Page 777 From angiotensinogen to Ang I: renin......Page 778 From Ang I to Ang II: ACE......Page 779 From Ang II to Ang-(1–7): ACE2......Page 780 Summary......Page 781 References......Page 782 Further Reading......Page 783 Caspases......Page 784 ADAM and AMAMTS Proteases......Page 785 Matrix Metalloproteinases......Page 786 Type II Transmembrane Trypsin-like Serine Proteases: Matriptase......Page 787 Concluding Remarks......Page 788 References......Page 789 The Lysosomal Compartment......Page 794 Autophagy......Page 795 Autophagy......Page 796 Amino acid signaling......Page 797 Gaucher disease......Page 798 Identification of the First Inborn Disease of the Lysosome......Page 799 Effects of Lysosomal Storage......Page 800 Coordination of Lysosomal Biogenesis and Autophagy – Revelations from Human Pathology......Page 801 Danon disease – an intrinsic disturbance of macroautophagy......Page 802 Energy metabolism in lysosomal diseases......Page 803 Action myoclonus-renal failure syndrome......Page 804 Deficiency of a Lysosomal Membrane Protein or Transporter......Page 805 Abnormal biogenesis of lysosomes is illustrated by Hermansky–Pudlak diseases (Type 1–9); Chédiak–Higashi disease and the.........Page 806 Lysosome-Related Organelles and the Osteoclast......Page 807 I-Cell Disease......Page 808 Cystinosis......Page 809 Modulating Substrate Biosynthesis (Substrate-Reduction Therapy)......Page 810 Hematopoietic Stem-Cell Transplantation......Page 811 Molecular therapy for Gaucher disease......Page 812 Therapeutic Stratagems for Lysosomal Diseases with Neurological Manifestations......Page 813 Gene Transfer......Page 814 (ii) Indirect use of vector-transduced autologous hematopoietic stem-cells which are re-infused......Page 815 Pathogenesis and Physiological Understanding......Page 816 References......Page 817 Introduction......Page 820 Physiology and Function of AT......Page 821 Mechanism of Deficiency in the Classical form of ATD......Page 822 Cellular Mechanisms of Liver Disease......Page 823 Cellular Responses to Misfolding of Mutant ATZ......Page 825 Therapies for ATD Liver Disease......Page 827 See also......Page 828 References......Page 829 FrontCover......Page 832 Encyclopedia of Cell Biology......Page 835 Editor-in-Chief......Page 837 Volume Editors......Page 839 Section Editors......Page 841 Contributors to Volume 2......Page 847 Contents of Volume 2......Page 853 Preface......Page 857 Cell Biology: An Overview......Page 859 Imaging the Cell......Page 863 Organelles......Page 864 Cytoskeleton and Motors......Page 865 Reference......Page 866 CryoEM Sample Consideration......Page 867 CryoEM Image Processing......Page 868 Resolution of CryoEM Density Maps......Page 869 CryoEM Model Building and Model Validation......Page 870 Identifying Different Populations Within a Heterogeneous Sample......Page 871 Conclusion......Page 873 References......Page 874 Relevant Website......Page 875 Scanning the Specimen......Page 876 Beam – Specimen Interactions......Page 877 A Brief History of SEM......Page 878 Labeling for SEM......Page 879 Merging SEM and TEM......Page 880 SEM of Subcellular Detail......Page 881 SEM and the Nuclear Envelope......Page 882 Further Reading......Page 883 Specimen Preparation Methods......Page 884 Microscopy......Page 886 Tomogram Reconstruction and 3D Image Analysis......Page 887 Techniques to Combine with Cryo-ET......Page 888 Examples......Page 889 Future Outlook......Page 890 References......Page 892 Relevant Websites......Page 893 Chemical Fixation......Page 894 Cryo-Immobilization and Freeze-Substitution......Page 896 Preembedding- and On-Section Labeling......Page 898 Whole Mount Labeling......Page 899 Freeze-Fracture Replica Labeling......Page 901 CLEM......Page 902 Immunogold Label Quantification and Labeling Specificity......Page 903 References......Page 904 Further Reading......Page 905 Orientation and Location of Region of Interest......Page 906 3D SEM Techniques......Page 907 Data Handling and Segmentation......Page 909 References......Page 911 Introduction – Fluorescent Proteins......Page 913 Fluorescent Proteins as Probes for Function......Page 914 Imaging Cells in Whole Organisms......Page 917 Technical Considerations for Live Imaging......Page 918 Looking Forward......Page 921 References......Page 922 Cell/Substrate Contact Regions......Page 924 TIR Combined with Polarization: Plasma