Molecular Cell Biology 5E (Lodish et al)

979 Pages·2003·55.79 MB·English

Molecular Cell Biology

Fifth Edition

Harvey Lodish (Massachusetts Institute of Technology)

Arnold Berk (U. of California, Los Angeles)

Paul Matsudaira (Massachusetts Institute of Technology)

Chris A. Kaiser (Massachusetts Institute of Technology)

Monty Krieger (Massachusetts Institute of Technology)

Matthew P. Scott (Stanford U.)

Lawrence Zipursky (U. of California, Los Angeles)

James Darnell (Rockefeller U.)
ii
Summary

Molecular Cell Biology provides a clear introduction to the techniques and experiments of scientists
past and present, showing how important discoveries led to the formation of the field's key concepts.
Since the publication of the Fourth Edition, fundamental principles have emerged from our
understanding of molecular cell biology. This Fifth Edition strives to present these principles clearly
while providing essential experimental information.
iii
New to this Edition

REORGANIZED AND REWRITTEN FOR A MORE DIRECT FOCUS ON CELLS AND CELLULAR
SYSTEMS. The new author team has reshaped the text to emphasize just those topics that fall within the scope of the
course, presenting them in a logical, teachable organization in seven parts:
Chemical and Molecular Foundations
Cell Organization and Biochemistry
Genetics and Molecular Biology
Cell Signalling
Membrane Trafficking
The Cytoskelon
Cell Cycle and Cell-Growth Control

In Part I Chemical and Molecular Foundations:
New Chapter 1, Life Begins with Cells provides a conceptual overview of the text.
Chapter 2, Chemical Foundations focuses on the chemical concepts most relevant to molecular cell biology, and
features a new section introducing the cellular building blocks (amino acids, nucleotides, carbohydrates, fatty acids, and
phospholipids).
Chapter 4, Basic Molecular Genetic Mechanisms, has been restructured to describe the basic mechanisms of
transcription, translation, and DNA replication and the molecular machines that carry out these processes. It introduces
the concept of transcriptional control and includes a brief discussion of gene control in bacteria.

In Part II, Cell Organization and Biochemistry (Chs. 5 through 8), students get an early introduction to core cell
biology topics such as basic cell membranes, structure, and function.
Chapter 6, Integrating Cells into Tissues features an earlier, expanded treatment of adhesive cell-cell and cell-matrix
interactions, preparing students to think about how cells relate to each other and their immediate surroundings.
Chapters on Transport of Ions and Small Molecules Across Cell Membranes and Cellular Energetics appear
earlier in the book (Chs. 7 & 8 now; 15 and 16 in the previous edition).

In Part III, Genetics and Molecular Biology:
Chapter 9, Molecular Genetic Techniques and Genomics offers streamlined coverage of genetic and recombinant
DNA techniques (Chs. 7 and 8 in the previous edition). Several examples of DNA microarray analysis to determine
genome-wide expression patterns are presented here and throughout the book.
Chapters 11 and 12, Transcriptional Control of Gene Expression and Post-Transcriptional Gene Control and
Nuclear Transport, now focus on eukaryotic cells. Coverage of prokaryotic gene control has been shifted to Chapter 4.

In Part IV, Cell Signaling, the new edition provides expanded treatment of signaling systems and their integration
within the whole cell/organism, with chapters on Signaling at the Cell Surface (Ch. 13), Signaling Pathways That
Control Gene Activity (Ch. 14), and Integration of Signals and Gene Controls (Ch. 15)

In Part V, Membrane Trafficking:
Chapters on Moving Proteins into Membranes and Organelles (Ch. 16) and Vesicular Traffic, Secretion, and
Endocytosis (Ch. 17) offer an expanded introduction to protein sorting (a single chapter in the previous edition)
New Chapter 18, Metabolism and Movement of Lipids provides expanded coverage of an often-overlooked class of
macromolecules, plus an elegant case study of the two-way interplay between basic molecular cell biology and
medicine.

In Part VII, Cell Cycle and Cell-Growth Control
Regulating the Eukaryotic Cell Cycle is now Chapter 21 immediately preceding the chapter on cell birth, lineage,
and death. This chapter contains a new section on molecular mechanisms that permit cells to undergo meiosis rather than
mitosis.
New Chapter 22, Cell Birth, Lineage and Death emphasizes the general role of asymmetric cell division in early
development, includes new coverage of C. elegans cell lineage, and describes cell-type specification in yeast and muscle
(from fourth edition Chapter 14).
iv
OTHER CONTENT REORGANIZATIONS
Some topics on DNA replication, repair, and recombination (formerly a separate chapter) are now incorporated in
other chapters where they fit naturally:
DNA replication is covered in Basic Molecular Genetic Mechanisms (Ch. 4)
DNA damage and repair is covered in Cancer (Ch. 23)
Coverage of topoisomerases and mechanisms of recombination has been substantially reduced and incorporated into
other chapters where relevant.

Material on gene control and development (fourth edition Chapter 14) and cell interactions in development (fourth
edition Chapter 23), has been refocused to emphasize how studies in development inform our understanding of basic cell
processes. This material has been placed in several appropriate chapters in the Fifth Edition (Chapters 6,14, 15, and 22.)

Material on nerve cells (fourth edition Chapter 21) is now covered in Chapters 7 and 17, along with other ion-transport
and vesicle-trafficking processes.

SIGNATURE FOCUS ON EXPERIMENTS ENHANCED
Molecular Cell Biology doesn't just catalog concepts. It provides a clear introduction to the techniques and experiments
of scientists past and present, showing how important discoveries led to the formation of the fields key concepts. The
authors' commitment to providing students with an experimental focus continues to drive the narrative wherever possible
in this fifth edition. As well, new ways of presenting the experimental approach to student include:
Students answer a research question by looking at real experimental data in new Analyze the Data problems that
conclude each chapter. In addition to these problems, the Fifth Edition includes real data throughout, wherever possible.
Updated Perspectives for the Future, at the conclusion of each chapter which explore potential applications of future
discoveries and unanswered questions that lie ahead for researchers.
Titles for experimental figures have been rewritten to emphasize the experimental results.

NEW WAYS OF SEEING MOLECULAR CELL BIOLOGY
Given the importance of visuals in cell biology, the Fifth Edition offers the following innovations to the art and media
program:
New Overview Figures throughout provide the reader with an overview of the details to come.
New pairing of diagrams with micrographs make as clear as possible for the student what they are seeing in the real
image.
Many more stepped-out figures illustrate important concepts
More consistent schematic depictions of structures and processes within and across chapters
Improved treatment of structural data through the consistent presentation of molecular models across the text
Expanded video resource library, with many new videos for instructors to use in lectures.
v
Media

WEB
Companion Web Site at www.whfreeman.com/lodish
For students, the site serves both as a free, 24-hour-a-day virtual study guide and as a bridge to the working world of cell
and molecular biologists. Features include:
Over 50 Animations. Developed by the authors, these narrated animations illustrate dynamic processes and events in
molecular cell biology. Media Connections icons in the book link relevant figures with their corresponding animations
on the Web site. All animations are visually consistent with the book illustrations.
Sixty Quicktime research videos. These clips from cutting-edge laboratories around the world show your students
what cells and cellular processes really look like.
Classic Experiments. Each of these 20 brief illustrated essays covers a groundbreaking molecular cell/biology
experiment, and describes how a researcher formed a hypothesis, developed an experiment to test the hypothesis, and
how this affected our current understanding.
Timed MCAT/GRE-style prep exams. Referenced to the text, these practice exams give students valuable test-taking
experience.

Also available,
Student CD, 0-7167-8875-6
Please note, this CD has the same material as the student Web site
Instructors For Instructors, the site offers specific ideas on using the electronic media for the book while teaching
from it, including:
Textbook illustrations, photos, and tables in JPEG and PowerPoint format, optimized for lecture presentation.
Labels have been enlarged and are in boldface type; complicated multistep illustration shave been separated into parts,
and colors are enhanced.
Solutions to all text problems.
Q&A/MCAT/GRE Reports that allow instructors to track students' progress.
Testing on Molecular Cell Biology Test Bank in Word files

Plus:
Online Update Service
Now there is a convenient way to bring the most important developments in molecular cell biology research--as reported
in NATURE Reviews Molecular Cell Biology--into your classroom. The Online Update Service gives you quick access
to all review articles published in NRMCB. Finding information relevant to the topics you cover is easy. Entries are
organized according to the chapter sections of Molecular Cell Biology, Fifth Edition. Links include a short description of
the article, the entire article in PDF format, and illustrations from each article in a projection-friendly format for use in
lectures.

PRESENTATION/ASSESSMENT
Instructor's CD-ROM, 0-7167-0065-4
Contains the following electronic content to allow instructors to create their own websites and presentations:
Textbook illustrations, photos, and tables in JPEG and PowerPoint format, optimized for lecture presentation.
Labels have been enlarged and are in boldface type; complicated multistep illustration shave been separated into parts,
and colors are enhanced.
Sixty Quicktime research videos. These videos from cutting-edge laboratories around the world show your students
what cells and cellular processes really look like. These videos come from cutting-edge laboratories around the world.
Video Guide provides description of video, run time, and the source of the video (researcher(s) and institution).
Over 50 Animations. Developed by the authors, these narrated animations illustrate dynamic processes and events in
molecular cell biology. Media Connections icons in the book link relevant figures with their corresponding animations
on the Web site. All animations are visually consistent with the book illustrations.

Overhead Transparency Set, 0-7167-0069-7
Contains 250 full-color images from the text optimized for classroom projection, including all overview figures.
vi
Supplements

FOR STUDENTS
Working with Molecular Cell Biology, Fifth Edition: A Study Companion and Solutions Manual, by Brian
Storrie, Eric Wong, Rich Walker, and Glenda Gillaspy, all of Virginia Polytechnic Institute and State University
Each chapter of the Study Companion will be divided into three parts:
Reviewing Concepts: Serves as a study and review resource, posing questions on key principles, concepts, and
experiments
Analyzing Experiments: Requires students to answer multi-part problems based on experimental data, and to apply
knowledge of concepts and techniques.
Solutions to Problems: Includes the worked-out solutions to the questions posed. In addition, the worked-out answers
to every end-of-chapter question from the text.

Student CD, 0-7167-8875-6
**Please note, this CD has the same material as the student website does**
Over 50 Animations. Developed by the authors, these narrated animations illustrate dynamic processes and events in
molecular cell biology. Media Connections icons in the book link relevant figures with their corresponding animations
on the Web site. All animations are visually consistent with the book illustrations.
Sixty Quicktime research videos. Drawn from cutting edge labs around the world, these videos show your students
what cells and cellular processes really look like.
Classic Experiments. Each of these 20 brief illustrated essays covers a groundbreaking molecular cell/biology
experiment, and describes how a researcher formed a hypothesis, developed an experiment to test the hypothesis, and
how this affected our current understanding.
Timed MCAT/GRE-style prep exams. Referenced to the text, these practice exams give students valuable test-taking
experience.

AVAILABLE PACKAGES
Text + Working With Molecular Cell Biology, 0-7167-6152-1
Text + MCAT Practice Test, 0-7167-2241-0
Text + Student CD, 0-7167-8886-1
vii
About the Authors

Harvey Lodish is Professor of Biology at the Massachusetts Institute of Technology and a member of the Whitehead
Institute for Biomedical Research. Dr. Lodish is also a member of the National Academy of Sciences and the American
Academy of Arts and Sciences and President (2004) of the American Society for Cell Biology. He is well known for his
work on cell membrane physiology, particularly the biosynthesis of many cell-surface proteins, and on the cloning and
functional analysis of several cell-surface receptor proteins, such as the erythropoietin and TGF_ receptors, and transport
proteins, including those for glucose and fatty acids. Dr. Lodish teaches undergraduate and graduate courses in cell
biology.

Arnold Berk is Professor of Microbiology, Immunology and Molecular Genetics and a member of the Molecular
Biology Institute at the University of California, Los Angeles. Dr. Berk is also a fellow of the American Academy of
Arts and Sciences. He is one of the original discoverers of RNA splicing and of mechanisms for gene control in viruses.
His laboratory studies the molecular interactions that regulate transcription initiation in mammalian cells, focusing
particular attention on transcription factors encoded by oncogenes and tumor suppressors. He teaches introductory
courses in molecular biology and virology and an advanced course in cell biology of the nucleus.

Paul Matsudaira is a member of the Whitehead Institute for Biomedical Research, Professor of Biology and
Bioengineering at the Massachusetts Institute of Technology, and Director of the WI/MIT BioImaging Center. His
laboratory studies the mechanics and biochemistry of cell motility and adhesion and has developed high speed, high-
through-put DNA analysis methods based on microfabricated chips. He organized the first biology course required of all
MIT undergraduates and teaches courses in undergraduate biology and graduate bioengineering at MIT.
viii

Chris A. Kaiser is a cell biologist and geneticist who has made fundamental contributions to understanding the basic
processes of intracellular protein folding and membrane protein trafficking. His laboratory at the Massachusetts Institute
of Technology, where he is Professor of Biology, studies how newly synthesized membrane and secretory proteins are
folded and sorted in the compartments of the secretory pathway. Dr. Kaiser teaches genetics to undergraduates and
graduate students at MIT.

Monty Krieger is Thomas D. & Virginia W. Cabot Professor in the Department of Biology at the Massachusetts
Institute of Technology. For his innovative teaching of undergraduate biology and human physiology as well as graduate
cell biology courses, he has received numerous awards. His laboratory has made contributions to our understanding of
membrane trafficking through the Golgi apparatus, and has cloned and characterized receptor proteins important for the
movement of cholesterol into and out of cells.

Matthew P. Scott is Professor of Developmental Biology and Genetics at Stanford University School of Medicine and
Investigator at the Howard Hughes Medical Institute. He is a member of the National Academy of Sciences and the
American Academy of Arts and Sciences and a past president of the Society for Developmental Biology. He is known
for his work in developmental biology and genetics, particularly in areas of cell-cell signaling and homeobox genes and
for discovering the roles of developmental regulators in cancer. Dr. Scott teaches development and disease mechanisms
to medical students and developmental iology to graduate students at Stanford University.
ix
Table of 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