New Insights into Cell and Membrane Transport Processes

I. Na+, K+, and H+ Transport.- 1 Molecular Properties of Voltage-Sensitive Sodium Channels.- 1. Introduction.- 2. Physiological Properties of Sodium Channels.- 3. Neurotoxins as Molecular Probes of Sodium Channels.- 4. Identification of Protein Components of Sodium Channels in Neurons.- 5. Molecular Size of the Sodium Channel.- 6. Protein Subunits of the Purified Sodium Channel.- 7. Reconstitution of Sodium Channel Function from Purified Components.- 8. The Amino Acid Sequence of the Sodium Channel as Inferred from cDNA Clones.- References.- II. Proton Pumps and Electrochemical Gradients.- 2 Studies of a Biological Energy Transducer: The lac Permease of Escherichia coli.- 1. Introduction.- 2. Morphology and Permeability of Proteoliposomes Reconstituted with lac Permease.- 3. A Single Polypeptide is Required for Lactose Transport.- 4. Reconstitution of Active Transport in Proteoliposomes Containing lac Permease and Cytochrome o Oxidase.- 5. Secondary Structure of lac Permease.- 6. Immunologic Reagents as Structure/Function Probes.- 7. Subunit Structure.- 8. Oligonucleotide-Directed Site-Specific Mutagenesis.- References.- 3 The Erythrocyre Anion-Exchange Protein: Primary Structure Deduced from the cDNA Sequence and a Model for Its Arrangement within the Plasma Membrane.- 1. Overview.- 2. Introduction.- 3. Materials and Methods.- 3.1. Isolation of cDNA Clones and DNA Sequencing.- 3.2. Computer-Assisted DNA Sequence Analysis.- 3.3. Cell Culture.- 3.4. RNA Blot Hybridization.- 4. Results.- 4.1. Mouse and Human Band 3 Share Sequence Homology.- 4.2. Band 3 Has Three Structural Domains.- 4.3. Band 3 Expression Is Regulated during Differentiation of MEL Cells.- 5. Discussion.- 5.1. Transmembrane Orientation of the Band 3 Polypeptide.- 5.2. Location of the H2DIDS-Binding Lysines in Band 3.- 5.3. The Structure and Mechanism of the Anion-Exchange Site.- References.- 4 The Lysosomal Proton Pump.- 1. Introduction.- 2. ATP-Dependent Acidification of Lysosomes.- 3. Characteristics of the Lysosomal Proton Pump.- 3.1. Electrogenicity.- 3.2. Inhibitors.- 3.3. Nucleotide Specificity.- 4. Lysosome Vesicles.- References.- 5 Ion PumpSy Ion Pathways, Ion Sites.- 1. Introduction.- 2. The Lysosomal H+ Pump.- 3. The H+ Pump of Renal Medulla.- 4. Gastric H+-K+ ATPase.- 4.1 “Resting” Vesicles.- 4.2. “Stimulated” Vesicles.- 5. The Ca2+ Pump of Rough Endoplasmic Reticulum.- 6. Pharmacology of the H+-K+ ATPase.- 6.1. Potassium Site Antagonists.- 6.2. Sulfhydryl Reagents.- References.- III. Calcium Channels and the Calcium Pump.- 6 Shifts between Modes of Calcium Channel Gating as a Basis for Pharmacologic Modulation of Calcium Influx in Cardiac, Neuronal, and Smooth-Muscle-Derived Cells.- 1. Introduction.- 2. Experimental Methods.- 3. Large-Conductance Ca2+ Channels in a Smooth Muscle Cell Line.- 4. Modal Activity and Bay K 8644 Response in A10 Cells and Sensory Neurons.- 5. Graded Shifts in the Balance between Modes.- 6. Modes of Gating as a Framework for Describing Modulatory Effects.- 7. Nimodipine as an Example of Ca2+ Antagonists That Stabilize Mode 0.- 8. ?-Adrenergic Stimulation Promotes Mode 1 Rather than Mode 2.- 9. Changes in Ca2+ Channel Inactivation with ?-Adrenergic Stimulation.- 10. How Similar are Large-Conductance Ca2+ Channels in Various Cell Types?.- 11. Distinguishing Between L-Type Ca2+ Channels and Other Types of Ca2+ Channels.- 12. Possible Differences among L-Type Ca2+ Channels.- 13. Calcium-Agonist-Promoted Mode 2 Gating: A General Property of L-Type Channels?.- 14. Questions about the Basis of Spontaneously Occurring Mode 2 Activity.- 15. Altered Balance between Modes of Channel Gating during ? Stimulation of Cardiac Ca2+ Channels.- 16. Comparison Between Up-Modulation by ? Agonists and Down-Modulation by Ca2+ Antagonists such as Nimodipine.- References.- 7 Chemical Pharmacology of Ca2+ Channel Ligands.- 1. Introduction.- 2. Specific Sites of Interaction for 1,4-Dihydropyridines.- 3. Topographic and Functional Relationship of Ligand-Binding Sites to Ca2+ Channels.- 4. Regulation of Ligand-Binding Sites and Function at the Calcium Channel.- 5. Conclusions and Prospective.- References.- 8 Information Flow in the Calcium Messenger System.- 1. Introduction.- 2. Calcium as Messenger.- 2.1. Calcium as Messenger during Sustained Cellular Response.- 2.2. Autoregulation of Cytosolic Calcium Concentration.- 2.3. Sensitivity Modulation.- 3. Two-Branch Model of Cell Activation.- 4. Validation of the Two-Branch System.- 4.1. Phosphotidylinositide Turnover.- 4.2. Cellular Calcium Metabolism.- 4.3. Patterns of Protein Phosphorylation.- 5. Role of Ca2+ in the Operation of the C-Kinase Branch.- 5.1. Calcium and Activation of C-Kinase.- 5.2. Calcium and C-Kinase Turnover Rate.- 5.3. Temporal Integration of Response.- 6. General Applicability of the Model.- 6.1. Peptide Hormone Secretion.- 6.2. Smooth Muscle Contraction.- 7. Alternative Modalities of Gain Control.- 8. Set Point Control by cAMP.- 9. Membrane Ca2+ Cycling as a General Regulatory Device.- References.- 9 Neutrophil Activation, Polyphosphoinositide Hydrolysis, and the Guanine Nucleotide Regulatory Proteins.- 1. Introduction.- 2. Biochemical Events Associated with Cellular Activation.- 3. Relevance of Polyphosphoinositide Hydrolysis to the Activation of the Neutrophils.- 3.1. Effects of Chemotactic Factors on Polyphosphoinositide Metabolism in the Neutrophils.- 3.2. Protein Kinase C and the Neutrophils.- 4. The Role of the Guanine-Nucleotide-Binding Regulatory Proteins in Signal Transduction and Calcium Mobilization in Neutrophils.- 5. Conclusions: A Model for Neutrophil Activation.- References.- IV. Inositol Lipids and the Calcium-Mediated Cellular Responses.- 10 Agonist-Dependent Phosphoinositide Metabolism: A Bifurcating Signal Pathway.- 1. Introduction.- 2. Formation of PIP2.- 3. Receptor Coupling of PIP2-Specific Phosphodiesterase: Possible Role of a G Protein.- 4. Inositol Trisphosphate and DO Formation.- 5. Second Messenger Mode of Action.- References.- 11 Hormone-Induced Inositol Lipid Breakdown and Calcium-Mediated Cellular Responses in Liver.- 1. Introduction.- 2. Inositol-1,4,5-Trisphosphate as a Calcium-Mobilizing Second Messenger.- 3. Hormone Effects on Ca2+ Fluxes.- 4. Summary.- References.- 12 Comparison of the Na+ Pump and the Ouabain-Resistant K+ Transport System with Other Metal Ion Transport ATPases.- 1. Introduction.- 2. ATP-Dependent Metal Ion Pumps.- 3. Sodium Pump Structure.- 4. Ouabain-Resistant K+ Transport System.- References.- 13 Current Concepts of Tumor Promotion by Phorbol Esters and Related Compounds.- 1. The Two-Stage Model of Carcinogenesis.- 2. Cellular Effects of Phorbol Esters and Membrane-Associated Receptors.- 3. Effects of Tumor Promoters on Protein Kinase C.- 4. Inhibition of Protein Kinase C by Tamoxifen.- 5. Substrates for Protein Kinase C.- 6. Compartmentalization of Protein Kinase C.- 7. Tumor Promotion, Growth Factors, and Oncogenes.- 8. Applied Aspects in Therapeutics.- References.- V. Cell Polarity and Membrane Transport Processes.- 14 Intracellular Protein Topogenesis.- References.- 15 Analysis of Epithelial Cell Surface Polarity Development with Monoclonal Antibodies.- 1. Introduction.- 2. Monoclonal Antibodies against the MDCK Cell Surface.- 3. Cell Surface Distribution of Membrane Glycoproteins.- 4. Tight Junctions and the Development of Cell Surface Polarity.- 5. Identification of Nephron-Segment-Specific Cell Surface Proteins.- 6. High-Resistance MDCK Cells as a Model for the Collecting Tubule.- References.- 16 Frequency and Time Domain Analysis of Epithelial Transport Regulation.- 1. Introduction.- 2. Differentiating between Possible Mechanisms of Transport Regulation.- 2.1. Impedence Analysis.- 2.2. Noise (Fluctuation) Analysis.- 2.3. Patch Clamp.- 3. Results Obtained from Frequency Domain Analysis.- 3.1. Membrane Area.- 3.2. Channel Density.- 3.3. Single-Channel Properties.- 4. Summary.- References.- 17 The Epithelial Sodium Channel.- 1. Introduction.- 2. Description of the Na+ Channel.- 2.1. Single-Channel Conductance.- 2.2. Selectivity.- 2.3. Current-Voltage Relationship.- 2.4. The Outer Mouth of the Channel.- 2.5. The Inner Mouth of the Channel.- 2.6. Single Filing.- 3. Regulation of the Na+ Channel.- 3.1. Regulation by External Na+.- 3.2. Regulation by Hormones.- 3.3. Other Factors.- 4. Conclusion.- References.- VI. Endocytosis as a Cell Transport Pathway.- 18 Uptake and Intracellular Processing of Cell Surface Receptors: Current Concepts and Prospects.- 1. Introduction.- 2. Clathrin-Coated Pits.- 3. The Role of the Clathrin Lattice.- 4. Receptor Recycling.- 5. Formation and Longevity of Coated Pits.- 6. Uptake from the Fluid Phase.- 7. The Endosome Compartment.- 8. Selective Routing of Ligands and Receptors.- 9. The Internalization of Effector Ligands.- 10. Conclusions.- References.- 19 Sorting in the Prelysosomal Compartment (CURL): Immunoelectron Microscopy of Receptors and Ligands.- 1. Introduction.- 2. Immunogold Detection of Receptors and Ligands.- 3. Ultrastructural Observations of Different Receptor Systems.- 3.1. The Asialoglycoprotein Receptor.- 3.2. The Mannose-6-Phosphate Receptor.- 3.3. The Polymeric IgA Receptor.- 3.4. Colocalization of ASGP-R, MP-R, and IgA-R.- 4. Concluding Remarks.- References.- 20 Mechanisms of Molecular Sorting in Endosomes.- 1. Introduction.- 2. Endosome Ontogeny and Morphology.- 2.1. The Life History of Endosomes.- 2.2. Three-Dimensional Structure of Endosomes and Lysosomes.- 3. Acidification of Endosomes.- 3.1. The Endosome H+ ATPase.- 3.2. Proton Translocation in Other Endocytic and Secretary Organelles.- 3.3. Acidification-Defective Mutant Cell Lines.- 3.4. Endosome Acidification Mutants Also Exhibit Altered Golgi Function.- 4. The Role of Endosome Acidity and Ligand Valency in Fe Receptor Transport.- 4.1. The Structure and Function of the Mouse Macrophage Fe Receptor.- 4.2. Ligand Valency and Fc Receptor Transport.- 4.3. The Role of Intravesicular pH in Fc Receptor Transport.- 4.4. Mechanisms of Molecular Sorting.- 5. Biochemistry of Endosomes and Lysosomes.- 5.1. The Isolation and Characterization of Endosomes and Lysosomes.- 5.2. Structure of the Lysosomal Membrane.- References.- 21 Transport of Protein Toxins across Cell Membranes.- 1. Introduction.- 2. Toxins That Affect Protein Synthesis.- 2.1. Diphtheria Toxin.- 2.2. The Toxin from Pseudomonas aeruginosa.- 2.3. Abrin, Ricin, Viscumin, and Modeccia.- 2.4. Shigella Toxin.- 3. Toxins That Activate Adenylate Cyclase.- 3.1. Cholera Toxin.- 3.2. Other Toxins That Affect Adenylate Cyclase.- 4. Neurotoxins.- 4.1. Tetanus Toxin.- 4.2. Botulinus Toxin.- 5. Conclusion.- References.