Cell and Molecular Biology

265 Pages·2018·209.766 MB·English

by  Nalini Chandar, Susan Viselli

Lippincott
Illustrated Reviews:
Cell and Molecular
Biology
Second Edition
Nalini Chandar, PhD
Professor of Biochemistry
Midwestern University
Downers Grove, Illinois
Susan Viselli, PhD
Professor of Biochemistry
Midwestern University
Downers Grove, Illinois
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Second Edition
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Library of Congress Cataloging-in-Publication Data
I
Names: Chandar, Nalini, author. Viselli, Susan, author.
Title: Cell and molecular biology I Nalini Chandar, Susan Viselli.
Other titles: Lippincott illustrated reviews.
I I I
Description: Second edition. Philadelphia :Wolters Kluwer, [2019] Series: Lippincott illustrated reviews Includes
index.
I
Identifiers: LCCN 2017054851 ISBN 9781496348500
I I I I I
Subjects: MESH: Cells Biological Transport-physiology Cell Physiological Phenomena Genetic Phenomena
I
Examination Questions Outlines
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Classification: LCC QH581.2 NLM QU 18.2 DDC 611/.0181--dc23 LC record available at https:/llccn.loc.
gov/2017054851
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Dedication
In memory of our parents. This book is dedicated to those
we teach and those who taught us.
Acknowledgments
We are grateful to the team at Wolters Kluwer. We thank Crystal Taylor whose support has
been invaluable throughout the course of the first and second editions of this book. We
also extend special thanks to Matt Chansky who expertly and patiently transformed our
sketches into the works of art that appear as figures throughout this book.
We value the support of our colleagues who read and critiqued early versions of the
chapters, who served as peer reviewers, and to those who have adopted this title for their
courses. We hope that this second edition will be a helpful resource to students of the
health professions.
In Memoriam
Richard A. Harvey, PhD
1936-2017
Cocreator and series editor of the Lippincott Illustrated Reviews series,
in collaboration with Pamela C. Champe, PhD (1945-2008).
Illustrator and coauthor of the first books in the series:
Biochemistry, Pharmacology, and Microbiology and Immunology.
Contents
UNIT I- Cell and Tissue Structure and Organization
Chapter 1: Stem Cells and Their Differentiation ... 2
Chapter 2: Extracellular Matrix and Cell Adhesion ... 11
Chapter 3: Biological Membranes ... 31
Chapter 4: Cytoskeleton ... 40
Chapter 5: Organelles ... 55
UNIT II- Organization of the Euknryotic Genome and Gene Expression
Chapter 6: The Eukaryotic Genome ...6 6
Chapter 7: DNA Replication ... 77
Chapter 8: Transcription ... 92
Chapter 9: Translation ... 102
Chapter 10: Regulation of Gene Expression ... 116
Chapter 11: Protein Trafficking ... 127
Chapter 12: Protein Degradation ... 138
UNIT III-Membrane Transport
Chapter 13: Basic Concepts of Transport ... 146
Chapter 14: Active Transport ... 155
Chapter 15: Glucose Transport ... 162
Chapter 16: Drug Transport ... 170
UNIT IV-Cell Signaling
Chapter 17: G-Protein Signaling ... 176
Chapter 18: Catalytic Receptor Signaling ... 185
Chapter 19: Steroid Receptor Signaling ... 194
UNIT V- Regulation of Cell Growth and Cell Death
Chapter 20: The Cell Cycle ... 204
Chapter 21: Regulation of the Cell Cycle ... 212
Chapter 22: Abnormal Cell Growth ... 221
Chapter 23: Cell Death ...2 31
Chapter 24: Aging and Senescence ... 244
lndex. .•2 53
iv
UNIT I
Cell and Tissue Structure
and Organization
Unity of plan everywhere lies hidden under the mask
of diversity of structure-the complex is everywhere evolved
out of the simple.
-Thomas Henry Huxley
A Lobster; or, the Study of Zoology (1861). In: Collected
Essays, Vol. 8. 1894: 205-206.
The most basic and simple form of human life is the cell. Complex
organisms, such as humans, are collections of these individual cells that
have grown and differentiated to generate the organism itself. Each cell
in an adult developed in a purposeful way from a precursor cell along a
specific lineage to become organized structurally and according to its
function. Be it a liver cell, a blood cell, a bone cell, or a muscle cell, it was
derived from a stem cell generated soon after the organism's conception.
Hidden within the tiny stem cell is the vast capacity to develop into an
array of diverse cell types that differentiate into efficient individual units
that survive only within the context of the whole person.
Our discussion of cell and molecular biology therefore begins with an
examination of stem cells, from which all other cells are generated. As we
move deeper into this unit, we explore structural components of tissues
including the extracellular matrix, which is produced by cells but resides
outside the boundary of cell membranes. In considering cell structure,
cell membranes serve as our starting point. As the outer limit of the
cell, the plasma membrane protects the cell's interior from the environ
ment. Yet, it is also a dynamic structure that enables interactions with the
environment and facilitates the cell's function. Within the confines of the
plasma membrane, we find cytoskeletal proteins that not only organize
the cytoplasm and provide a structural framework for the cell but also
function in the intracellular movement of chromatin and organelles. The
organelles are specialized centers within each cell that carry out func
tional processes, including energy extraction in the mitochondria, mac
romolecule digestion in the lysosomes, and DNA and RNA synthesis in
the nucleus. While each organelle is a complex machine in its own right
and has its own unique role within the cell, organelles are linked physi
cally by the cytoskeleton and cooperate in completing their tasks with a
unified purpose.
1
Stem Cells and Their
Differentiation
I. OVERVIEW
All cells within an organism are derived from precursor cells. Precursor
cells divide along specific paths in order to produce cells that are differenti
ated to perform specialized tasks within tissue--s and organs. Cells with the
capacity to give rise to the whole organism are referred to as stem cells.
Stem cells remain undifferentiated ana are c aracterized by the ability to
self-renew. They also generate many daaghter cells committed to differen
tiate (change) into a diverse range of specialized cell types. A daughter cell
with the ability to differentiate info a wide variety of cell types is pluripotent.
The human body is made up of al<>out 200 different types of cells. The
human genome is the same i all cell types, meaning that within an
individual person, all cells Have exactly the same DNA sequences and
genes. Stem cells represent all the different ways that human genes can
be expressed as proteins. In order for different regions of the genome
to be expressed in crtterent cell types, the genome has to be reversibly
modified. In fact, the organization of chromatin (a complex of specific
proteins an QNA) varies between cell types and is made possible by
reversible covalent modification of the proteins that are associated with
DNA and sometimes the DNA itself (see also Chapter 6). These modifi
eations are important to expose regions of the DNA to the proteins and
e~ymes that are required for transcription (DNA ➔ RNA), allowing for
variation in gene expression as proteins (see also Chapter 8).
Different cell types arise from precursor cells that proliferate (divide) and
eventually differentiate into cells with unique structures, functions, and
chemical composition. From specific proteins produced in the cells, a
special type of cell division, and the microenvironment of the precursor
cell, a progeny of cells is produced. This progeny can both sustain the
organism and carry out specific functions in the body.
II. STEM CELLS
Stem cells exist in both early embryos and adult tissues (Figure 1.1 ). The
stem cells present in early embryos have an extensive capacity to differ
entiate into all cell types of the organism. Populations of stem cells also
exist in adults and can differentiate into various cells within a lineage but
not outside that lineage. For example, a hematopoietic stem cell (HSC)
can differentiate into various types of blood cells but not into a hepatocyte
(liver cell). However, researchers may have found new properties of adult
2
II. Stem Cells 3
.Tot ipotent
a-cell
stage
..... .....
..
Egg 4-cell
stage,
totipotent
cells
,________~, '~ ~ ~ ~ ~
Epidermis Neurons Pigment Cardiac Skeletal Kidney Red Bone Pancreatic Thyroid Liver Sperm Egg
cells muscle muscle tubule blood cells- cell cells cells
cells cells cells osteoblasts
'-----------------i[ Unipotent Jr----------------------'
Figure 1.1
Embryonic and adult stem cells.
stem cells, which under certain conditions allow differentiation into more
cell types than previously recognized.
• Totipotency is the potential of a single cell to develop into a
total organism (e.g., a fertilized egg and the four-cell stage).
• Pluripotency is a cell's capacity to give rise to all cell types
in the body but not to the supporting structures, such as the
placenta, amnion, and chorion, all of which are needed for
the development of an organism.
• Multi potency is a cell's capacity to give rise to a small num
ber of different cell types.
• Unipotency is a cell's capacity to give rise to only one cell
type.
A. Pluripotent stem cells
The most primitive, undifferentiated cells in an embryo are embry
onic stem cells (ESCs). These cells are derived from the inner cell
mass of preimplantation embryos (Figure 1.1) and can be maintained
in the pluripotent state in vitro. They can give rise to all the three germ
layers (ectoderm, mesoderm, and endoderm) with the ability to dif
ferentiate into a number of cell types. This ability to differentiate into
multiple cell types is called plasticity (Figure 1.2).
4 1. Stem Cells and Their Differentiation
B. Unipotent stem cells
Cells that reside within adult tissues and retain the ability to generate
cells for the tissue type to which they belong are unipotent. Under
normal situations, unipotent stem cells give rise to only one cell type.
For example, a myoblast (muscle cell precursor) can give rise to a
myocyte (muscle cell), and a hepatoblast (liver cell precursor) can
give rise to a hepatocyte (liver cell).
C. Multipotent stem cells
Adult multipotent stem cells have been identified for a number of dif
ferent tissue types such as brain, bone marrow, peripheral blood,
blood vessels, skeletal muscle, skin, and liver (Figure 1.2).
1. Hematopoietic stem cells: This group of stem cells gives rise
to all the types of blood cells, including red blood cells, B lympho
cytes, T lymphocytes, natural killer cells, neutrophils, basophils,
eosinophils, monocytes, macrophages, and platelets.
Figure 1.2
2. Mesenchymal stem cells: Also called bone marrow stromal
Adult stem cell plasticity.
cells, mesenchymal cells give rise to a variety of cell types, includ
ing osteoblasts (bone cells), chondrocytes (cartilage cells), adipo
cytes (fat cells), and other kinds of connective tissue.
3. Skin stem cells: These stem cells are found in the basal layer of
the epidermis and also at the base of hair follicles. Epidermal stem
cells give rise to keratinocytes, while the follicular stem cells give
rise to both hair follicles and the epidermis.
4. Neural stem cells: Stem cells in the brain can differentiate into its
three major cell types: nerve cells (neurons) and two types of non
neuronal cells-astrocytes and oligodendrocytes.
5. Epithelial stem cells: Located in the lining of the digestive tract,
epithelial stem cells are found in deep crypts and give rise to sev
eral cell types, including absorptive cells, goblet cells, Paneth cells,
and enteroendocrine cells.
Ill. STEM CELL COMMITMENT
Most stem cells first become intermediate progenitor cells (also known as
transit amplifying cells), which then produce a differentiated population of
cells. A good example of this stepwise process is illustrated by HSCs. HSCs
are multipotent but undergo commitment into a particular pathway in a step
wise process. In the first step, they give rise to two different progenitors. The
committed progenitors then undergo many rounds of cell division to produce
a population of cells of a given specialized type. In this particular case, the
HSCs give rise to one type that is capable of generating lymphoid cells and
another type that results in the generation of myeloid cells (Figure 1.3).
The different steps of commitment happen due to changes in gene
expression. Genes for a particular pathway are switched on, while access
to other developmental pathways is shut off by specific proteins that bind
DNA and act as transcription factors (see Chapter 10 ). These proteins
are able to both activate the genes necessary for a particular pathway
and shut down the expression of genes necessary for development along
a different pathway.