Preface

• “Molecules, Cells, and Model Organisms” (Chapter 1) is an improved and expanded introduction to cell biology. It retains the overviews of evolution, molecules, different forms of life, and model organisms used to study cell biology found in previous editions. In this edition, it also includes a survey of eukaryotic organelles, which was previously found in Chapter 9.

• “Culturing and Visualizing Cells” (Chapter 4) has been moved forward (previously Chapter 9) as the techniques used to study cells become ever more important. Light-sheet microscopy, super-resolution microscopy, and two-photon excitation microscopy have been added to bring this chapter up to date.

• All aspects of mitochondrial and chloroplast structure and function have been collected in “Cellular Energetics” (Chapter 12). This chapter now begins with the structure of the mitochondrion, including its endosymbiotic origin and organelle genome (previously in Chapter 6). The chapter now discusses the role of mitochondria-associated membranes (MAMs) and communication between mitochondria and the rest of the cell.

• Cell signaling has been reframed to improve student accessibility. “Signal Transduction and G Protein–Coupled Receptors” (Chapter 15) begins with an overview of the concepts of cell signaling and methods for studying it, followed by examples of G protein–coupled receptors performing multiple roles in different cells. “Signaling Pathways That Control Gene Expression” (Chapter 16) now focuses on gene expression, beginning with a new discussion of Smads. Further examples cover the major signaling pathways that students will encounter in cellular metabolism, protein degradation, and cellular differentiation. Of particular interest is a new section on Wnt and Notch signaling pathways controlling stem-cell differentiation in planaria. The chapter ends by describing how signaling pathways are integrated to form a cellular response in insulin and glucagon control of glucose metabolism.

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  FIGURE 4-21 Two-photon excitation microscopy allows deep penetration for intravital imaging. (a) In conventional point-scanning confocal microscopy, absorption of a single photon results in an electron jumping to the excited state. In two-photon excitation, two lower-energy photons arrive almost instantaneously and induce the electron to jump to the excited state. (b) Two-photon microscopy can be used to observe cells up to 1 mm deep within a living animal immobilized on the microscope stage. (c) Neurons in a lobster were imaged using two-photon excitation microscopy.

  [Part (c) unpublished data from Peter Kloppenburg and Warren R. Zipfel.]

• Our new co-author, Kelsey C. Martin, has extensively revised and updated “Cells of the Nervous System” (Chapter 22) to include several new developments in the field. Optogenetics, a technique that uses channelrhodopsins and light to perturb the membrane potential of a cell, can be used in live animals to link neural pathways with behavior. The formation and pruning of neural pathways in the central nervous system is under active investigation, and a new discussion of signals that govern these processes focuses on the cell-cell contacts involved. This discussion leads to an entirely new section on learning and memory, which explores the signals and molecular mechanisms underlying synaptic plasticity.

• Model organisms Chlamydomonas reinhardtii (for study of flagella, chloroplast formation, photosynthesis, and phototaxis) and Plasmodium falciparum (novel organelles and a complex life cycle) (Ch. 1)

• Intrinsically disordered proteins (Ch. 3)

• Chaperone-guided folding and updated chaperone structures (Ch. 3)

• Unfolded proteins and the amyloid state and disease (Ch. 3)

• Hydrogen/deuterium exchange mass spectrometry (HXMS) (Ch. 3)

• Phosphoproteomics (Ch. 3)

• Two-photon excitation microscopy (Ch. 4)

• Light-sheet microscopy (Ch. 4)

• Super-resolution microscopy (Ch. 4)

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  Figure 5-19 (a) Translating nucleic acid sequence into amino acid sequence requires two steps. Step 1: An aminoacyl-tRNA synthetase couples a specific amino acid to its corresponding tRNA. Step 2: The anticodon base-pairs with a codon in the mRNA specifying that amino acid. (b) Molecular model of the human mitochondrial aminoacyl-tRNA synthetase for Phe in complex with tRNA^Phe.

• Three-dimensional culture matrices and 3D printing (Ch. 4)

• Ribosome structural comparison across domains shows conserved core (Ch. 5)

• CRISPR–Cas9 system in bacteria and its application in genomic editing (Ch. 6)

• Chromosome conformation capture techniques reveal topological domains in chromosome territories within the nucleus (Ch. 8)

• Mapping of DNase I hypersensitive sites reveals cell developmental history (Ch. 9)

• Long noncoding RNAs involved in X inactivation in mammals (Ch. 9)

• ENCODE databases (Ch. 9)

• Improved discussion of mRNA degradation pathways and RNA surveillance in the cytoplasm (Ch. 10)

• Nuclear bodies: P bodies, Cajal bodies, histone locus bodies, speckles, paraspeckles, and PML nuclear bodies (Ch. 10)

• GLUT1 molecular model and transport cycle (Ch. 11)

• Expanded discussion of the pathway for import of PTS1-bearing proteins into the peroxisomal matrix (Ch. 13)

• Expanded discussion of Rab proteins and their role in vesicle fusion with target membranes (Ch. 14)

• Human G protein–coupled receptors of pharmaceutical importance (Ch. 15)

• The role of Smads in chromatin modification (Ch. 16)

  

  FIGURE 6-43b Cas9 uses a guide RNA to identify and cleave a specific DNA sequence.

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  FIGURE 16-31 Gradients of Wnt and Notum guide regeneration of a head and tail by planaria.

  [Part (b) Jessica Witchley and Peter Reddien.]

• Wnt concentration gradients in planarian development and regeneration (Ch. 16)

• Inflammatory hormones in adipose cell function and obesity (Ch. 16)

• Regulation of insulin and glucagon function in control of blood glucose (Ch. 16)

• Use of troponins as an indicator of the severity of a heart attack (Ch. 17)

• Neurofilaments and keratins involved in skin integrity, epidermolysis bullosa simplex (Ch. 18)

• New structures and understanding of function of dynein and dynactin (Ch. 18)

• Expanded discussion of lamins and their role in nuclear membrane structure and dynamics during mitosis (Ch. 18)

• Diseases associated with cohesin defects (Ch. 19)

• The Hippo pathway (Ch. 19)

• Spindle checkpoint assembly and nondisjunction and aneuploidy in mice; nondisjunction increases with maternal age (Ch. 19)

• Expanded discussion of the functions of the extracellular matrix and the role of cells in assembling it (Ch. 20)

• Mechanotransduction (Ch. 20)

• Structure of cadherins and their cis and trans interactions (Ch. 20)

• Cadherins as receptors for class C rhinoviruses and asthma (Ch. 20)

• Improved discussion of microfibrils in elastic tissue and in LTBP-mediated TGF-β signaling (Ch. 20)

• Tunneling nanotubes (Ch. 20)

• Functions of WAKs in plants as pectin receptors (Ch. 20)

• Pluripotency of mouse ES cells and the potential of differentiated cells derived from iPS and ES cells in treating various diseases (Ch. 21)

• Pluripotent ES cells in planaria (Ch. 21)

• Cells in intestinal crypts that dedifferentiate to replenish intestinal stem cells (Ch. 21)

• Cdc42 and feedback loops that control cell polarity (Ch. 21)

• Prokaryotic voltage-gated Na⁺ channel structure, allowing comparison with voltage-gated K⁺ channels (Ch. 22)

• Optogenetics techniques for linking neural circuits with behavior (Ch. 22)

• Mechanisms of synaptic plasticity that govern learning and memory (Ch. 22)

  

  FIGURE 22-8 Neurogenesis in the adult brain. Newly born neurons were labeled with GFP in the dentate gyrus of control mice and mice that were allowed to exercise on a running wheel.

  [Chunmei Zhao and Fred H. Gage.]

• Inflammasomes and non-TLR nucleic acid sensors (Ch. 23)

• Expanded discussion of somatic hypermutation (Ch. 23)

• Improved discussion of the MHC molecule classes; MHC-peptide complexes and their interactions with T-cells (Ch. 23)

• Lineage commitment of T cells (Ch. 23)

• Tumor immunology (Ch. 23)

• The characteristics of cancer cells and how they differ from normal cells (Ch. 24)

• How carcinogens lead to mutations and how mutations accumulate to cancer (Ch. 24)

• Stereoisomers of small molecules as drugs—sterically pure molecules have different effects from mixtures (Ch. 2)

• Cholesterol is hydrophobic and must be transported by lipoprotein carriers LDL and HDL (Ch. 2)

• Essential amino acids must be provided in livestock feed (Ch. 2)

• Saturated, unsaturated, and trans fats: their molecular structures and nutritional consequences (Ch. 2)

• Protein misfolding and amyloids in neurodegenerative diseases such as Alzheimer’s and Parkinson’s (Ch. 3)

• Small molecules that inhibit enzyme activity can be used as drugs (aspirin) or in chemical warfare (sarin gas) (Ch. 3)

• Small-molecule inhibitors of the proteasome are used to treat certain cancers (Ch. 3)

• Disruptions of GTPases, GAPs, GEFs, and GDIs by mutations and pathogens cause a wide variety of diseases (Ch. 3)

• 3-D printing technology may be used to grow replacement organs (Ch. 4)

• The high-resolution structures of ribosomes can help identify small-molecule inhibitors of bacterial, but not eukaryotic, ribosomes (Ch. 5)

• Mutations in mismatch repair proteins lead to hereditary nonpolyposis colorectal cancer (Ch. 5)

• Nucleotide excision-repair proteins were identified in patients with xeroderma pigmentosum (Ch. 5)

• Human viruses HTLV, HIV-1, and HPV initiate infection by binding to specific cell-surface molecules, and some integrate their genomes into the host cell’s DNA (Ch. 5)

• The sickle-cell allele is an example of one that exhibits both dominant and recessive properties depending on the phenotype being examined (Ch. 6)

• DNA microarrays can be useful as medical diagnostic tools (Ch. 6)

• Recombinant DNA techniques are used to mass-produce therapeutically useful proteins such as insulin and G-CSF (Ch. 6)

• Most cases of genetic diseases are caused by inherited rather than de novo mutations (Ch. 6)

• A CFTR knockout mouse line is useful in studying cystic fibrosis (Ch. 6)

• ABO blood types are determined by the carbohydrates attached to glycoproteins on the surfaces of erythrocytes (Ch. 7)

• Atherosclerosis, marked by accumulation of cholesterol, other lipids, and other biological substances in an artery, is responsible for the majority of deaths due to cardiovascular disease in the United States (Ch. 7)

• Microsatellite repeats have a tendency to expand and can cause neuromuscular diseases such as Huntington disease and myotonic dystrophy (Ch. 8)

• L1 transposable elements can cause genetic diseases by inserting into new sites in the genome (Ch. 8)

• Exon shuffling can result in bacterial resistance to antibiotics, a growing challenge in hospitals (Ch. 8)

• The NF1 gene, which is mutated in patients with neurofibromatosis, is an example of how bioinformatics techniques can be used to identify the molecular basis of a genetic disease (Ch. 8)

• Telomerase is abnormally activated in most cancers (Ch. 8)

• TFIIH subunits were first identified based on mutations in those subunits that cause defects in DNA repair associated with a stalled RNA polymerase (Ch. 9)

• HIV encodes the Tat protein, which inhibits termination of transcription by RNA polymerase II (Ch. 9)

• Synthetic oligonucleotides are being used in treatment of Duchenne muscular dystrophy (DMD)(Ch. 10)

• Mutations in splicing enhancers can cause exon skipping, as in spinal muscular atrophy (Ch. 10)

• Expansion of microsatellite repeats in genes expressed in neurons can alter their relative abundance in different regions of the central nervous system, resulting in neurological disorders (Ch. 10)

• Thalassemia commonly results from mutations in globin-gene splice sites that decrease splicing efficiency but do not prevent association of the pre-mRNA with snRNPs (Ch. 10)

• Genes encoding components of the mTORC1 pathway are mutated in many cancers, and mTOR inhibitors combined with other therapies may suppress tumor growth (Ch. 10)

• Aquaporin 2 levels control the rate of water resorption from urine being formed by the kidney (Ch. 11)

• Certain cystic fibrosis patients are being treated with a small molecule that allows a mutant protein to traffic normally to the cell surface (Ch. 11)

• SGLT2 inhibitors are in development or have been approved for treatment of type II diabetes (Ch. 11)

• Antidepressants and other therapeutic drugs, as well as drugs of abuse, target Na⁺-powered symporters because of their role in the reuptake and recycling of neurotransmitters (Ch. 11)

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• Drugs that inhibit the Na⁺/K⁺ ATPase in cardiac muscle cells are used in treating congestive heart failure (Ch. 11)

• Oral rehydration therapy is a simple, effective means of treating cholera and other diseases caused by intestinal pathogens (Ch. 11)

• Mutations in CIC-7, a chloride ion channel, result in defective bone resorption characteristic of the hereditary bone disease osteopetrosis (Ch. 11)

• The sensitivity of mitochondrial ribosomes to the aminoglycoside class of antibiotics, including chloramphenicol, can cause toxicity in patients (Ch. 12)

• Mutations and large deletions in mtDNA cause certain diseases, such as Leber’s hereditary optic neuropathy and Kearns-Sayre syndrome (Ch. 12)

• Cyanide is toxic because it blocks ATP production in mitochondria (Ch. 12)

• Reduction in amounts of cardiolipin, as well as an abnormal cardiolipin structure, results in the heart and skeletal muscle defects and other abnormalities that characterize Barth’s syndrome (Ch. 12)

• Reactive oxygen species are by-products of electron transport that can damage cells (Ch. 12)

• ATP/ADP antiporter activity was first studied over 2000 years ago through the examination of the effects of poisonous herbs (Ch. 12)

• There are two related subtypes of thermogenic fat cells (Ch. 12)

• A hereditary form of emphysema results from misfolding of proteins in the endoplasmic reticulum (Ch. 13)

• Autosomal recessive mutations that cause defective peroxisome assembly can lead to several developmental defects often associated with craniofacial abnormalities, such as those associated with Zellweger syndrome (Ch. 13)

• Certain cases of cystic fibrosis are caused by mutations in the CFTR protein that prevent movement of this chloride channel from the ER to the cell surface (Ch. 14)

• Study of lysosomal storage diseases has revealed key elements of the lysosomal sorting pathway (Ch. 14)

• The hereditary disease familial hypercholesterolemia results from a variety of mutations in the LDLR gene (Ch. 14)

• Therapeutic drugs using the TNFα-binding domain of TNFα receptor are used to treat arthritis and other inflammatory conditions (Ch. 15)

• Monoclonal antibodies that bind HER2 and thereby block signaling by EGF are useful in treating breast tumors that overexpress HER2 (Ch. 15)

• The agonist isoproterenol binds more strongly to epinephrine-responsive receptors on bronchial smooth muscle cells than does epinephrine, and is used to treat bronchial asthma, chronic bronchitis, and emphysema (Ch. 15)

• Some bacterial toxins (e.g., Bordetella pertussis, Vibrio cholerae, certain strains of E. coli) catalyze a modification of a G protein in intestinal cells, increasing intracellular cAMP, which leads to loss of electrolytes and fluids (Ch. 15)

• Nitroglycerin decomposes to NO, a natural signaling molecule that, when used to treat angina, increases blood flow to the heart (Ch. 15)

• PDE inhibitors elevate cGMP in vascular smooth muscle cells and have been developed to treat erectile dysfunction (Ch. 15)

• Many tumors contain inactivating mutations in either TGF-β receptors or Smad proteins and are resistant to growth inhibition by TGF-β (Ch. 16)

• Epo and G-CSF are used to boost red blood cells and neutrophils, respectively, in patients with kidney disease and during certain cancer therapies that affect blood cell formation in the bone marrow (Ch. 16)

• Many cases of SCID result from a deficiency in the IL-2 receptor gamma chain and can be treated by gene therapy (Ch. 16)

• Mutant Ras proteins that bind but cannot hydrolyze GTP, and are therefore locked in an active GTP-bound state, contribute to oncogenic transformation (Ch. 16)

• Potent and selective inhibitors of Raf are being clinically tested in patients with melanomas caused by mutant Raf proteins (Ch. 16)

• The deletion of the PTEN gene in multiple types of advanced cancers results in the loss of the PTEN protein, contributing to the uncontrolled growth of cells (Ch. 16)

• High levels of free β-catenin, caused by aberrant hyperactive Wnt signaling, are associated with the activation of growth-promoting genes in many cancers (Ch. 16)

• Inappropriate activation of Hh signaling associated with primary cilia is the cause of several types of tumors (Ch. 16)

• Increased activity of ADAMs can promote cancer development and heart disease (Ch. 16)

• The brains of patients with Alzheimer’s disease accumulate amyloid plaques containing aggregates of the Aβ₄₂ peptide (Ch. 16)

• Diabetes mellitus is characterized by impaired regulation of blood glucose, which can lead to major complications if left untreated (Ch. 16)

• Hereditary spherocytic anemias can be caused by mutations in spectrin, band 4.1, and ankyrin (Ch. 17)

• Duchenne muscular dystrophy affects the protein dystrophin, resulting in progressive weakening of skeletal muscle (Ch. 17)

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• Hypertrophic cardiomyopathies result from various mutations in proteins of the heart contractile machinery (Ch. 17)

• Blood tests that measure the level of cardiac-specific troponins are used to determine the severity of a heart attack (Ch. 17)

• Some drugs (e.g., colchicine) bind tubulin dimers and restrain them from polymerizing into microtubules, whereas others (e.g., taxol) bind microtubules and prevent depolymerization (Ch. 18)

• Defects in LIS1 cause Miller-Dieker lissencephaly in early brain development, leading to abnormalities (Ch. 18)

• Some diseases, such as ADPKD and Bardet-Biedl syndrome, have been traced to defects in primary cilia and intraflagellar transport (Ch. 18)

• Keratin filaments are important to maintaining the structural integrity of epithelial tissues by mechanically reinforcing the connections between cells (Ch. 18)

• Mutations in the human gene for lamin A cause a wide variety of diseases termed laminopathies (Ch. 18)

• In cohesinopathies, mutations in cohesion subunits or cohesion loading factors disrupt expression of genes critical for development, resulting in limb and craniofacial abnormalities and intellectual disabilities (Ch. 19)

• Aneuploidy leads to misregulation of genes and can contribute to cancer development (Ch. 19)

• Aneuploid eggs are largely caused by chromosome mis-segregation in meiosis I or nondisjunction, leading to miscarriage or Down syndrome (Ch. 19)

• The protein CDHR3 enables class C rhinoviruses (RV-C) to bind to airway epithelial cells, enter them, and replicate, causing respiratory diseases and exacerbating asthma (Ch. 20)

• The cadherin desmoglein is the predominant target of autoantibodies in the skin disease pemiphigus vulgaris (Ch. 20)

• Some pathogens, such as hepatitis C virus and the enteric bacterium Vibrio cholerae, have evolved to exploit the molecules in tight junctions (Ch. 20)

• Mutations in connexin genes cause a variety of diseases (Ch. 20)

• Defects in the glomerular basement membrane can lead to renal failure (Ch. 20)

• In cells deprived of ascorbate, the pro-α collagen chains are not hydroxylated sufficiently to form the structural support of collagen necessary for healthy blood vessels, tendons, and skin, resulting in scurvy (Ch. 20)

• Mutations affecting type I collagen and its associated proteins cause a variety of diseases, including osteogenesis imperfecta (Ch. 20)

• A variety of diseases, often involving skeletal and cardiovascular abnormalities (e.g., Marfan syndrome), result from mutations in the genes encoding the structural proteins of elastic fibers or the proteins that contribute to their proper assembly (Ch. 20)

• Connections between the extracellular matrix and cytoskeleton are defective in muscular dystrophy (Ch. 20)

• Leukocyte-adhesion deficiency is caused by a genetic defect that results in the leukocytes’ inability to fight infection, thereby increasing susceptibility to repeated bacterial infections (Ch. 20)

• The stem cells in transplanted bone marrow can generate all types of functional blood cells, which makes such transplants useful for patients with certain hereditary blood diseases as well as cancer patients who have received irradiation or chemotherapy (Ch. 21)

• Channelopathies, including some forms of epilepsy, are caused by mutations in genes that encode ion channels (Ch. 22)

• The topical anesthetic lidocaine works by binding to amino acid residues along the voltage-gated Na⁺ channel, locking it in the open but occluded state (Ch. 22)

• The cause of multiple sclerosis is not known, but seems to involve either the body’s production of auto-antibodies that react with myelin basic protein or the secretion of proteases that destroy myelin proteins (Ch. 22)

• Peripheral myelin is a target of autoimmune disease, mainly involving the formation of antibodies against P_o (Ch. 22)

• The key role of VAMP in neurotransmitter exocytosis can be seen in the mechanism of action of botulinum toxin (Ch. 22)

• Neurotransmitter transporters are targets of a variety of drugs of abuse (e.g., cocaine) as well as therapeutic drugs commonly used in psychiatry (e.g., Prozac, Zoloft, Paxil) (Ch. 22)

• Nicotinic acetylcholine receptors produced in brain neurons are important in learning and memory; loss of these receptors is observed in schizophrenia, epilepsy, drug addiction, and Alzheimer’s disease (Ch. 22)

• Studies suggest that the voltage-gated Na⁺ channel Nav1.7 is a key component in the perception of pain (Ch. 22)

• People vary significantly in sense of smell (Ch. 22)

• Synaptic translation of localized mRNAs is critical to the formation and the experience-dependent plasticity of neural circuits, and alterations in this process result in neurodevelopmental and cognitive disorders (Ch. 22)

• The immunosuppressant drug cyclosporine inhibits calcineurin activity through the formation of a cyclosporine-cyclophilin complex, thus enabling successful allogenic tissue transplantation (Ch. 23)

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• Vaccines elicit protective immunity against a variety of pathogens (Ch. 23)

• Increased understanding of the molecular cell biology of tumors is revolutionizing the way cancers are diagnosed and treated (Ch. 24)

• Vascular plants have rigid cell walls and use turgor pressure to stand upright and grow (Ch. 11)

• Transgenic plants have been produced that overexpress the vacuolar Na⁺/H⁺ antiporter, and can therefore grow successfully in soils containing high salt concentrations (Ch. 11)

• Editing of plant mitochondrial RNA transcripts can convert cytosine residues to uracil residues (Ch. 12)

• Photosynthesis is an important process for synthesizing ATP (Ch. 12)

• Chloroplast DNAs are evolutionarily younger and show less structural diversity than mitochondrial DNAs (Ch. 12)

• Chloroplast transformation has led to engineered plants that are resistant to infections as well as plants that can be used to make protein drugs (Ch. 12)

• In giant green algae such as Nitella, the cytosol flows rapidly due to use of myosin V (Ch. 17)

• Formation of the spindle and cytokinesis have unique features in plants (Ch. 18)

• Meristems are niches for stem cells in plants (Ch. 21)

• A negative feedback loop maintains the size of the shoot apical stem-cell population (Ch. 21)

• The root meristem resembles the shoot meristem in structure and function (Ch. 21)