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Molecular Cell Biology 5th ed - Lodish et al

Contents


1. Life Begins with Cells
• Completely rewritten chapter that highlights the common structural and functional properties of cells despite
their various sizes, shapes, and specialized abilities
• The contribution of experimental approaches from various disciplines to an integrated view of the cell
• Which model organisms are most suited for particular studies and why
• Insights drawn from genomics concerning evolution and their implication for the study of human diseases
• 1.1 The Diversity and Commonality of Cells
• 1.2 The Work of Cells
• 1.3 Investigating Cells and Their Constituents
• 1.4 Choosing the Right Experimental Organism
• 1.5 A Genome Perspective on Evolution
2. Chemical Foundations
• Emphasis on role of noncovalent bonds and molecular complementarity in interactions between
macromolecules
• Consolidated introduction to properties of biological monomers and principles of their polymerization
• Introduction to phospholipids and their assembly into larger structures
• Brief review of chemical equilibrium and relation to steady state, binding reactions, pH, and buffers Coverage
of free energy, coupled reactions, energy coupling, and role of electron carriers in redox reactions
• 2.1 Atomic Bonds and Molecular Interactions
• 2.2 Cellular Building Blocks
• 2.3 Chemical Equilibrium
• 2.4 Biochemical Energetics
3. Protein Structure and Function
• Concise description of levels of protein structure with emphasis on use of recurring motifs and domains
• Brief discussion of antibodies to illustrate specificity of ligand binding by proteins
• New coverage of physical association of enzymes in a common pathway and evolution of multifunctional
enzymes
• Increased focus on proteins as molecular machines and motors with moving parts (conformational changes)
and as macromolecular assemblies whose complexity permits emergence of new properties with specific
examples
• Expanded discussion of mechanisms for regulating protein activity including the role of Ca2-calmodulin, G
proteins, and kinase/phosphatase combinations as molecular switches
• Common techniques presented in one section at end of chapter
• 3.1 Hierarchical Structure of Proteins
• 3.2 Folding, Modification, and Degradation of Proteins
• 3.3 Enzymes and the Chemical Work of Cells
• 3.4 Molecular Motors and Machines
• 3.5 Common Mechanisms for Regulating Protein Function
• 3.6 Purifying, Detecting, and Characterizing Proteins

4. From Gene to Protein: Basic Molecular Genetic Mechanisms
• Description of the macromolecular assemblies that carry out transcription, translation, and DNA replication
• Updated models of the ribosome
• Improved process figures of transcription, translation, and DNA replication
• Clearer description of bidirectional chain growth of leading and lagging strands from single DNA replication
origin
• Earlier discussion of gene control, focusing on prokaryotic mechanisms as prelude for later coverage of more
complex eukaryotic mechanisms
• Overview of the structure and life cycles of viruses
• 4.1 Structure of Nucleic Acids
• 4.2 Transcription of Protein-Coding Genes and Formation of Functional mRNA
• 4.3 Control of Bacterial Gene Expression
• 4.4 The Three Roles of RNA in Translation
• 4.5 Stepwise Synthesis of Proteins on Ribosomes
• 4.6 DNA Replication
• 4.7 Viruses: Parasites of the Cellular Genetic System
5. Biomembranes and Cell Architecture
• Consolidated coverage of the structures and properties of membrane lipids and proteins
• New material on lipid rafts and lipid-binding motifs in peripheral proteins
• Expanded section on the cytoskeleton, providing an early introduction to the three classes of cytoskeletal fibers
and their organization within cells
• Techniques for isolating subcellular structures and the uses of different types of microscopy covered at end of
the chapter
• Three-dimensional models based on computational reconstructions of digital micrographs
• 5.1 Biomembranes: Lipid Composition and Structural Organization
• 5.2 Biomembranes: Protein Components and Basic Functions
• 5.3 Organelles of the Eukaryotic Cell
• 5.4 The Cytoskeleton: Components and Structural Functions
• 5.5 Purification of Cells and Their Parts
5.6 Visualizing Cell Architecture
6. Integrating Cells into Tissues
• Early coverage of adhesive interactions that cells aggregate into tissues
• New overview section outlining major types of adhesive molecules in animals and how their diversity arises
• Presentation of all types of cell junctions in epithelial and nonepithelial cells integrated into one chapter
• Increased emphasis on the role of integrins and of cell-surface adhesive molecules in linking the extracellular
matrix to the cytoskeleton and signaling pathways, thereby mediating inside-out and outside-in effects
• Updated description of tight junctions and variations in their permeability
• New material on how diverse functions of glycosaminoglycans (GAGs) are determined
• Expanded discussion of integrins including new molecular models of active and inactive states
• New coverage of dystrophin glycoprotein complex (DGC), which is critical to structural integrity of muscle
cells
• Brief coverage of cell cultures with examples of their use in research and to produce monoclonal antibodies
• Numerous medical, plant, and biotech applications

• 6.2 Sheetlike Epithelial Tissues: Junctions and Cell-Adhesion Molecules
• 6.3 The Extracellular Matrix of Epithelial Sheets
• 6.4 The Extracellular Matrix of Nonepithelial Tissues
• 6.5 Adhesive Interactions Involving Nonepithelial Cells
• 6.6 Plant Tissues
• 6.7 Growth and Use of Cultured Cells
7. Transport of Ions and Small Molecules across Cell Membranes
• Clear comparison of different transport mechanisms and basic principles of protein-mediated transport
• Updated molecular models of muscle Ca2 ATPase, lipid flippase, resting K channel, aquaporin, voltage-gated
K channel and implications for their operation
• Expanded coverage of ABC superfamily of transporters (e.g., bacterial permeases, mammalian MDR proteins)
• Coverage of the generation and transmission of electric signals by neurons, an instructive example of the
complex interplay of various transport proteins in carrying out complex physiological functions
• 7.1 Overview of Membrane Transport
• 7.2 ATP-Powered Pumps and the Intracellular Ionic Environment
• 7.3 Nongated Ion Channels and the Resting Membrane Potential
• 7.4 Cotransport by Symporters and Antiporters
• 7.5 Movement of Water
• 7.6 Transepithelial Transport
• 7.7 Voltage-Gated Ion Channels and the Propagation of Action Potentials in Nerve Cells
• 7.8 Neurotransmitters and Transport Proteins in Signal Transmission at Synapses
8. Cellular Energetics
• Integrated coverage of ATP generation driven by the proton-motive force in bacterial, animal, and plant cells
• New coverage of the evolutionary origin of mitochondria and chloroplasts
• Clear explanation of the Q cycle and new molecular model of CoQ-cytochrome c reductase complex explaining
its operation in the cycle
• More detailed description of proton movement through F0F1 complex including an updated model for how the
protein operates to produce ATP
• Discussion of recent model for the supramolecular organization of the two plant photosystems and regulation
of their relative activities
• 8.1 Oxidation of Glucose and Fatty Acids to CO2
• 8.2 Electron Transport and Generation of the Proton-Motive Force
• 8.3 Harnessing the Proton-Motive Force for Energy-Requiring Processes
• 8.4 Photosynthetic Stages and Light-Absorbing Pigments
• 8.5 Molecular Analysis of Photosystems
• 8.6 CO2 Metabolism during Photosynthesis

9. Molecular Genetic Techniques and Genomics
• Reorganized and streamlined discussion of classical genetic and recombinant DNA techniques for identifying
genes and determining their function
• Coverage of newer techniques including epitope tagging to localize proteins, expanded discussion of DNA
microarrays, and computer searching of sequence banks
• Consolidated coverage of methods for inactivating specific genes including RNA interference (RNAi) and
dominant-negative alleles
• Applications of and insights derived from genomics
• Separate section on inherited human diseases and general approach for discovering their molecular causes
• 9.1 Genetic Analysis of Mutations to Identify and Study Genes
• 9.2 DNA Cloning by Recombinant DNA Methods
• 9.3 Characterizing and Using Cloned DNA Fragments
• 9.4 Genomics: Genome-Wide Analysis of Gene Structure and Expression
• 9.5 Inactivating the Function of Specific Genes in Eukaryotes
• 9.6 Identifying and Locating Human Disease Genes
10. Gene and Chromosome Structure
• Updated estimates of the amounts of various types of noncoding ("nonfunctional") DNA in the human genome
• Updated model for movement of LINE sequences, the most numerous type of nonfunctional DNA in mammals
• Exon shuffling and the evolutionary significance of noncoding DNA
• Various uses of fluorescent in situ hybridization (FISH) to detect specific chromosomes or sequences within
them
• Telomeric sequences and role of telomerase in preventing chromosome shortening during DNA replication
• 10.1 Molecular Definition of a Gene
• 10.2 Chromosomal Organization of Genes and Noncoding DNA
• 10.3 Mobile DNA
• 10.4 Structural Organization of Eukaryotic Chromosomes
• 10.5 Morphology and Functional Elements of Eukaryotic Chromosomes
• 10.6 Organelle DNAs
11. Transcriptional Control of Gene Expression
• Focus on gene control in eukaryotes (prokaryotes covered in Chapter 4)
• New molecular model of yeast RNA polymerase II and comparison with bacterial RNA polymerase
• New coverage of concept that a "histone code" functions in controlling transcription initiation by modulating
chromatin structure
• New information and expanded discussion about the structure and function of the mediator complex in
transcription initiation
• Recent model of ordered binding of multiple activators and co-activators during transcription initiation
• Yeast two-hybrid system for detecting proteins that interact

• 11.2 Regulatory Sequences in Protein-Coding Genes
• 11.3 Activators and Repressors of Transcription
• 11.4 Transcription Initiation by RNA Polymerase II and Other Polymerases
• 11.5 Molecular Mechanisms of Transcription Activation and Repression
• 11.6 Control of Transcription-Factor Activity of Nuclear Receptors
12. Post-Transcriptional Controls and Nuclear Transport
• Evidence for coupling of RNA synthesis and processing
• New coverage of role of SR proteins in determining splicing sites in RNA
• General function of splicing repressors and activation
• Updated, expanded discussion of transport through nuclear pores, FG-nucleoporins, and commonalities in
export and import mechanisms
• New coverage of repression of mRNA translation by microRNAs, RNA interference, and alternative pathways of
mRNA degradation
• Recently discovered mechanism of cytoplasmic polyadenylation and its role in early development and nervous
system (e.g., memory, learning)
• 12.1 RNA Chain Elongation and Termination
• 12.2 Processing of Eukaryotic Pre-mRNA
• 12.3 Regulation of mRNA Processing
• 12.4 Macromolecular Transport across the Nuclear Envelope
• 12.5 Cytoplasmic Mechanisms of Post-Transcriptional Control
• 12.6 Processing of rRNA and tRNA
13. Signaling at the Cell Surface
• Two overview sections focusing on general concepts applicable to all or nearly all signaling pathways with
summary table of major receptor/signaling pathways
• Revamped discussion of signaling from G protein-coupled receptors (GPCRs) including the muscarinic
acetylcholine receptor in cardiac muscle and transducin in retinal cells
• New molecular model of trimeric G proteins in active and inactive conformations
• Use of fluorescence energy transfer to detect interacting proteins (e.g., receptor and coupled G protein) in
living cells
• Examples of GPCR pathways that regulate transcription of genes
• 13.1 Signaling Molecules and Cell-Surface Receptors (3200)
• 13.2 Intracellular Signal Transduction (2000)
• 13.3 GPCRs That Activate or Inhibit Adenylyl Cyclase
• 13.4 GPCRs That Directly or Indirectly Regulate Ion Channels
• 13.5 GPCRs That Activate Phospholipase C
• 13.6 Activation of Gene Transcription by GPCRs

14. Signaling Pathways That Control Gene Activity
• Expanded, integrated coverage of signaling from TGF receptors, cytokine receptors, and receptor tyrosine
kinases
• Experimental identification of Jaks and Stats as signal-transduction proteins
• New coverage on regulating signaling from cytokine receptors
• Emphasis that some receptors can activate multiple signaling pathways
• Additional material on recruitment of signaling proteins to the plasma membrane
• Updated discussion of NF-kB signaling pathway and its numerous functions in cells
• New section on bone resorption as a case study of the integration of multiple molecular mechanisms (cell
adhesion, membrane transport, and signaling between cells) in one physiological process
• Role of presenilin in normal signaling from Notch receptor and its likely contribution to pathology of
Alzheimer's disease
• 14.1 TGF Receptors and the Direct Activation of Smads
• 14.2 Cytokine Receptors and the JAK-STAT Pathway
• 14.3 Receptor Tyrosine Kinases and Activation of Ras
• 14.4 MAP Kinase Pathways
• 14.5 Phosphoinositides As Signal Transducers from RTKs and Cytokine Receptors
• 14.6 Pathways That Involve Signal-Induced Protein Cleavage
15. Integrating Signals with Gene Controls
• New chapter focusing on coordinated cell responses to environmental and development signals
• Coverage of techniques for determining changes in gene expression that produce cell responses to signals
• New section on oxygen deprivation as example of a program of cellular responses induced by an environmental
signal
• Involvement of signaling pathways in determining cell fates and boundaries during early development
• Enhanced discussion of early events in dorsoventral patterning of embryo
• Emphasis on evolutionary conserved signaling mechanisms and their functioning in different contexts (e.g., role
of Toll-like signaling in innate immunity in plants and animals; evolutionary relation of Hedgehog signaling to
sterol metabolism)
• 15.1 Experimental Approaches for Building a Comprehensive View of Signal-Induced Responses
• 15.2 Control of Cells by Environmental Influences
• 15.3 Control of Cell Fates by Graded Amounts of Regulators
• 15.4 Boundary Creation by Different Combinations of Transcription Factors in Adjacent Cells
• 15.5 Boundary Creation by Extracellular Signals
• 15.6 Reciprocal Induction and Lateral Inhibition
• 15.7 Integrating and Controlling Signals

16. Moving Proteins into Membranes and Organelles
• Focus on common elements in protein targeting: signal sequences and their receptors, structure of
translocation channels, and energy source that drives translocation
• New coverage of post-translational translocation into the endoplasmic reticulum (ER)
• Expanded discussion of topogenic sequences in membrane proteins synthesized on the endoplasmic reticulum
and use of hydrophobicity profiles to identify them
• Role of various protein-folding catalysts (e.g., BiP, Hsc proteins) in protein folding and translocation into
organelles
• New coverage of bacterial systems for moving proteins into the periplasmic space or across both the inner and
outer membrane
• Updated information on formation and rearrangement of disulfide bonds in eukaryotic and bacterial cells and
the unfolded-protein response
• Expanded, updated treatment of protein import to submitochondrial compartments and the corresponding
signal sequences
• New evidence that peroxisomal matrix and membrane proteins are imported by different pathways
• Clearer, more instructive figures of translocation pathways
• 16.1 Translocation of Secretory Proteins across the ER Membrane
• 16.2 Insertion of Proteins into the ER Membrane
• 16.3 Protein Modifications, Folding, and Quality Control in the ER
• 16.4 Export of Bacterial Proteins
• 16.5 Sorting of Proteins to Mitochondria and Chloroplasts
• 16.6 Sorting of Peroxisomal Proteins
17. Vesicular Traffic, Secretion, and Endocytosis
• Reorganized discussion of vesicle trafficking in the secretory pathway emphasizing mechanistic commonality of
different transport steps
• New section on relevant experimental techniques
• Expanded discussion of the role of GTPase switch proteins in formation and docking of transport vesicles
• New coverage of special pathways for delivering plasma-membrane proteins and cytoplasmic components to
lysosomes for degradation
• New information on molecular mechanism of virus budding from infected cells and its similarity to the
formation of multivesicular endosomes

• 17.1 Techniques for Studying the Secretory Pathway
• 17.2 Molecular Mechanisms of Vesicular Traffic
• 17.3 Vesicle Traffic in the Early Stages of the Secretory Pathway
• 17.4 Protein Sorting and Processing in Later Stages of the Secretory Pathway
• 17.5 Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins
• 17.6 Synaptic Vesicle Function and Formation

18. Metabolism and Movement of Lipids
• New chapter that provides an in-depth example of synergistic relationship between basic molecular cell biology
and medicine
• Assay for detecting flippase activity of ABC proteins
• Role of ABC proteins and other transport proteins in formation of bile and enterohepatic circulation
• Composition, formation, and transport of lipoproteins
• Discovery of LDL receptor and experiments demonstrating receptor-mediated endocytosis of LDL particles
• SREBP pathway for controlling cellular cholesterol levels; role of cholesterol-sensing SCAP protein and
regulated intramembrane proteolysis
• Development of atherosclerosis as a consequence of normal processes that provide defense against infection
and tissue damage
• Cell biological explanation of why some cholesterol is "good" and some is "bad"
• Rationale design of cholesterol-lowering drugs
• 18.1 Synthesis and Intracellular Movement of Membrane Lipids
• 18.2 Intercellular Lipid Transport
• 18.3 Regulation of Cellular Lipid Metabolism
• 18.4 The Cell Biology of Atherosclerosis, Heart Attacks, and Strokes
19. Cytoskeleton I: Microfilaments and Intermediate Filaments
• Support of cellular membranes by actin filaments, intermediate filaments, and linking proteins
• Role of cytoskeletal rearrangements in changes in cell shape and cellular movement
• Assay for myosin motor activity
• Functions of different myosins in vesicle trafficking, cytoplasmic streaming, and muscle contraction
• Control of cytoskeleton and cell migration by external signals
• 19.1 Actin Structures
• 19.2 The Dynamics of Actin Assembly
• 19.3 Myosin-Powered Cell Movements
• 19.4 Cell Locomotion
• 19.5 Intermediate Filaments
20. Cytoskeleton II: Microtubules
• Updated coverage of proteins that regulate microtubule assembly and cross-linkage
• New information about microtubule motor proteins and their cargoes
• Microtubule rearrangements and motor proteins during mitosis
• 20.1 Microtubule Organization and Dynamics
• 20.2 Kinesin- and Dynein-Powered Movements
• 20.3 Microtubule Dynamics and Motor Proteins during Mitosis

21. Regulating the Eukaryotic Cell Cycle
• Coverage of the cell cycle and its regulation shifted to immediately precede new chapter on cell birth, lineage,
and death
• Focus on the master controllers, the heterodimeric protein kinases that regulate the activities of multiple
proteins involved in DNA replication and mitosis
• Recent results leading to more complete understanding of molecular mechanisms that control entry into
anaphase
• Expanded discussion of checkpoints at which progression through the cell cycle is monitored with much new
information about their operation
• New section on proteins that direction a cell to undergo meiosis rather than mitosis and that mediate crossing
over
• 21.1 Overview of the Cell Cycle and Its Control
• 21.2 Biochemical Studies with Oocytes, Eggs, and Early Embryos
• 21.3 Genetic Studies with S. pombe
• 21.4 Molecular Mechanisms for Regulating Mitotic Events
• 21.5 Genetic Studies with S. cerevisiae
• 21.6 Cell-Cycle Control in Mammalian Cells
• 21.7 Checkpoints in Cell-Cycle Regulation
• 21.8 Meiosis: A Special Type of Cell Division
22. Cell Birth, Lineage, and Death
• New chapter providing integrated view of how different cell types arise, differentiate, and in some cases die
during early development
• Importance and properties of various stem-cell populations
• Crucial role of asymmetric cell division in development using C. elegans lineage as an example
• Current understanding of mechanisms for generating two different daughter cells during cell division
• Common molecular pathway leading to cell suicide due to lack of survival signals (e.g., neurotrophins) or to
cell murder due to killing signals (e.g., TNF and Fas ligand) from other cells
• 22.1 The Birth of Cells
• 22.2 Cell-Type Specification in Yeast
• 22.3 Specification and Differentiation of Muscle
• 22.4 Regulation of Asymmetric Cell Division
• 22.5 Cell Death and Its Regulation

23. Cancer
• Revised discussion with emphasis on multiple genetic changes leading to abnormal, unregulated cell
proliferation
• Expanded coverage and summarizing figure of signaling components that are mutated in various types of
cancer
• Use of DNA microarrays to detect subtle differences in different types of cancer cells
• Clearer explanation of inherited versus noninherited forms of cancer
• Development of Gleevec, a new anticancer drug, and why it works
• Updated description of role of p53 in G1 checkpoint and effects of its loss Addition of coverage on DNA
damage and repair
• Association of cancer development with some normal DNA-repair systems and defects in other repair systems
• 23.1 Tumor Cells and the Onset of Cancer
• 23.2 The Genetic Basis of Cancer
• 23.3 Oncogenic Mutations in Growth-Promoting Proteins
• 23.4 Mutations Causing Loss of Growth-Inhibiting and Cell-Cycle Controls
• 23.5 The Role of Carcinogens and DNA Repair in Cancer

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