医学细胞生物学 MEDICAL CELL BIOLOGY（英文原版改编版）（留学生与双语教学用）

Cell Biology is the most taught basic science course in medical school as it is one of the most rapidly
developing subjects in science. Cell biology overlaps with molecular biology, histology, pathology, cancer
biology, neuroscience, and many other major related disciplines. Having an up-to-date Cell Biology
textbook that covers many functional aspects is essential for medical students to “cross the bridge”
between basic sciences and clinical courses.
This textbook was edited and modified from Medical Cell Biology, Steven R. Goodman ed., Elsevier,
2008. The first several chapters serve as comprehensive introductions into organelle structure, functions
and gene expression. The second half of this book details many topics in medical science, including cell
signaling pathways, cell cycle, programmed cell death, and cancer. New technologies such as atomic force microscopy, proteomics, and gene therapy are also covered.

 

Cell Biology is the most taught basic science course in medical school as it is one of the most rapidly
developing subjects in science. Cell biology overlaps with molecular biology, histology, pathology, cancer
biology, neuroscience, and many other major related disciplines. Having an up-to-date Cell Biology
textbook that covers many functional aspects is essential for medical students to “cross the bridge”
between basic sciences and clinical courses.
This textbook was edited and modified from Medical Cell Biology, Steven R. Goodman ed., Elsevier,
2008. The first several chapters serve as comprehensive introductions into organelle structure, functions
and gene expression. The second half of this book details many topics in medical science, including cell
signaling pathways, cell cycle, programmed cell death, and cancer. New technologies such as atomic force microscopy, proteomics, and gene therapy are also covered.

Chapter 1 Tools of the Cell Biologist……………………….1
MICROSCOPY: ONE OF THE EARLIEST TOOLS
OF THE CELL BIOLOGIST……………………………….. 1
MORE TOOLS OF CELL BIOLOGY……………………. 11
SUMMARY………………………………………………………….16
SUGGESTED READINGS……………………………………. 16
Chapter 2 Cell Membranes……………………………………. 17
THE MOLECULAR STRUCTURE OF CELL
MEMBRANE…………………………………………………… 19
MEMBRANE TRANSPORT OF SMALL
MOLECULES………………………………………………….. 27
SUMMARY…………………………………………………………. 31
SUGGESTED READINGS……………………………………. 32
Chapter 3 Cytoskeleton………………………………………….. 33
MICROFILAMENTS……………………………………………. 33
INTERMEDIATE FILAMENTS…………………………… 40
MICROTUBULES………………………………………………… 43
SUMMARY…………………………………………………………. 48
SUGGESTED READINGS……………………………………. 48
Chapter 4 Organelle Structure and Function……… 49
THE NUCLEUS…………………………………………………… 50
ENDOPLASMIC RETICULUM…………………………… 51
THE GOLGI COMPLEX………………………………………. 66
ENDOCYTOSIS, ENDOSOMES, AND
LYSOSOMES…………………………………………………… 73
MITOCHONDRIA………………………………………………. 77
PEROXISOMES…………………………………………………… 87
SUMMARY…………………………………………………………. 88
SUGGESTED READINGS……………………………………. 89
Chapter 5 Cell Nucleus and Gene Expression……… 90
CELL NUCLEUS…………………………………………………. 90
DNA REPLICATION AND REPAIR ARE
CRITICAL NUCLEAR FUNCTIONS………………. 98
GENE EXPRESSION………………………………………….. 104
SUMMARY……………………………………………………….. 116
SUGGESTED READINGS………………………………….. 116
Chapter 6 Cell Adhesion and the Extracellular
Matrix………………………………………………….. 117
CELL ADHESION……………………………………………… 117
INTERCELLULAR JUNCTIONS……………………….. 119
CELL ADHESION HAS MANY IMPORTANT
ROLES IN TISSUE FUNCTION…………………….. 128
CELL ADHESION RECEPTORS TRANSMIT
SIGNALS THAT REGULATE CELL
BEHAVIOR……………………………………………………………….133
EXTRACELLULAR MATRIX…………………………….. 134
SUMMARY………………………………………………………..140
SUGGESTED READINGS………………………………….. 141
Chapter 7 Intercellular Signaling……………………….. 142
GENERAL MODES OF INTERCELLULAR
SIGNALING………………………………………………….. 142
HORMONES……………………………………………………… 144
XII 医学细胞生物学Meeddiiccaall Ceellll Biioollooggyy
GROWTH FACTORS………………………………………… 146
GASES: NITRIC OXIDE AND CARBON
MONOXIDE………………………………………………….. 148
NEUROTRANSMITTERS………………………………….. 150
SUMMARY……………………………………………………….. 154
SUGGESTED READINGS………………………………….. 155
Chapter 8 Cell Signaling Events………………………….. 156
SIGNALING IS OFTEN MEDIATED BY CELLSURFACE
RECEPTORS………………………………… 156
RECEPTOR TYROSINE KINASES AND RASDEPENDENT
SIGNAL TRANSDUCTION…… 157
SIGNALING BY CATALYTIC RECEPTORS/
SERINE-THREONINE KINASES………………….. 160
SIGNALING BY NONKINASE RECEPTORS……. 163
SIGNALING BY G-PROTEIN-COUPLED
RECEPTORS INVOLVES CLEAVAGE
OF GUANOSINE TRIPHOSPHATE TO
GUANOSINE DIPHOSPHATE…………………….. 166
SIGNALING BY STEROID HORMONE
RECEPTORS REQUIRES LIGAND
INTERACTION WITHIN THE
CYTOPLASM OR NUCLEUS……………………….. 167
OTHER SIGNALING PATHWAYS
SIGNALING BY THE RENINANGIOTENSIN-
ALDOSTERONE SYSTEM….169
SIGNALING BY THE JAK/STAT PATHWAY….. 170
CALCIUM/CALMODULIN SIGNAL
TRANSDUCTION…………………………………………. 170
SIGNALING BY ION CHANNEL RECEPTORS……….171
SUMMARY……………………………………………………….. 172
SUGGESTED READINGS………………………………….. 172
Chapter 9 The Cell Cycle and Cancer………………… 173
CELL CYCLE: HISTORY…………………………………… 173
THE CELL CYCLE IS REGULATED BY
CYCLIN AND RELATED PROTEINS…………… 174
MITOSIS……………………………………………………………. 176
MEIOSIS …………………………………………………………… 179
SENSORS RECOGNIZE SITES OF DNA
DAMAGE……………………………………………………… 181
CELL-CYCLE ALTERATIONS AND CANCER ……….183
SUMMARY……………………………………………………….. 184
SUGGESTED READINGS………………………………….. 184
Chapter 10 Programmed Cell Death…………………… 185
DISTINCT FORMS OF PROGRAMMED CELL
DEATH…………………………………………………………. 186
NEUROTROPHIN RECEPTORS……………………….. 189
CASPASES………………………………………………………… 191
SIGNALING PATHWAYS THAT PROMOTE
CELL SURVIVAL………………………………………….. 197
APOPTOSIS AND HUMAN DISEASE………………. 200
SUMMARY……………………………………………………….. 201
SUGGESTED READINGS………………………………….. 201

Cell Biology is the most taught basic science course in medical school as it is one of the most rapidly
developing subjects in science. Cell biology overlaps with molecular biology, histology, pathology, cancer
biology, neuroscience, and many other major related disciplines. Having an up-to-date Cell Biology
textbook that covers many functional aspects is essential for medical students to “cross the bridge”
between basic sciences and clinical courses.
This textbook was edited and modified from Medical Cell Biology, Steven R. Goodman ed., Elsevier,
2008. The first several chapters serve as comprehensive introductions into organelle structure, functions
and gene expression. The second half of this book details many topics in medical science, including cell
signaling pathways, cell cycle, programmed cell death, and cancer. New technologies such as atomic force microscopy, proteomics, and gene therapy are also covered.
Unlike many other general-purpose Cell Biology textbooks, this one is more medically oriented.We decided to keep all chapters in this edited version from the original book. In our edit, however, weremoved some graduate level material, as it would be either too sophisticated, or covered by other courses(histology, pathology, etc.). Students in China generally take Cell Biology in their freshmen year, so wewould like to give students a thoroughunderstanding of basic concepts.We felt that it was proper to also add several important topics. Much progress has been made in ourfield. Advances in single-cell technologies, induced pluripotent stem cells (iPSC), epigenetic modifications,and revelations in next generation sequencing make it almost impossible to cover everything necessarywithout restructuring.We realized that a concise, tailor-made version of a widely used textbook can be an excellent toolfor medical students. However, creating such a resource required hard work and dedication from manyfaculty members. Most of the editors have been teaching cell biology for more than 10 years, and manyhave doctoral degrees on cell biology or related subjects.I hope this book will give you just a snapshot of the ever-changing world of life sciences. Best of luckand we hope you find your journey into cell biology filled with fascination and exhilaration.
LI Guang
Professor and Chairwoman
Department of Genetics
College of Basic Medical Sciences
Tianjin Medical University
July 22, 2018
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Chapter

1

Tools of the Cell Biologist

one
One of the first questions a cell biologist might ask
in his or her search for a protein’s function would
be, “Where is it located in the cell?”
Is it in the
nucleus or the cytoplasm? Is it a surface membrane
protein, or resident in one of the cytoplasmic
organelles? Knowing the subcellular localization of
a protein provides significant direction for further
experiments designed to learn its function.

One of the primary tools a cell biologist would
use to answer the question of subcellular location
would be a microscope.

MICROSCOPY: ONE OF

THE EARLIEST

TOOLS OF THE

CELL BIOLOGIST

Microscopy, in its various forms, has historically
been the primary way in which investigators have
examined the appearance and substructure of cells,
and increasingly in recent decades, the location and
movement of biological molecules within cells. We
may speak broadly of two kinds of microscopy,
light microscopy (LM) and electron microscopy (EM),
although the field of microscopy recently has been
broadened by the advent of atomic force microscopy
(AFM).

The resolution of standard light microscopy is
limited by the wavelength of visible light, which is
comparable with the diameter of some subcellular
organelles; but a variety of contemporary techniques
now exist that permit light microscopic visualization
of proteins and nucleic acid molecules. Chief among
these new techniques are those using either organic
fluorescent molecules or quantum nanocrystals
(“quantum dots”) to directly or indirectly “tag”

individual macromolecules. Once the molecules of
interest have been fluorescently tagged, their cellular
location can be viewed via fluorescence microscopy
(Figure 1-1).

Fluorescence Microscopy

In many situations, fluorescence microscopy
is the first approach one might take to identify
the subcellular location of particular proteins.
One widely used technique to fluorescently tag a
protein is based on the great precision and high
affinity with which an antibody molecule can bind
its cognate protein antigen. This antibody-based
approach has been termed immunolabeling.

Because antibodies are relatively large
molecules that do not cross the surface membrane
of living cells, one must fix and permeabilize cells
before an antibody can be used to view the location
of a target protein. In recent years, it has become
possible to view the location and movement of
fluorescently tagged proteins inside living cells,
using an approach that has been broadly termed
genetic tagging. With this approach, one uses
genetic engineering to create a plasmid expressing
the protein of interest, which has been fused at its
amino or carboxy terminus with either a directly
fluorescent tag, such as green fluorescent protein
(GFP), or an indirect fluorescent tag, such as tetra-
cysteine. Tetra-cysteine-tagged proteins when
expressed in cells can bind subsequently added
small, membrane-permeable fluorescent molecules
such as the red or green biarsenicals FlAsH and
ReAsH. The lines between immunolabeling and
genetic tagging blur when one considers another
type of genetic tagging, termed epitope-tagging, in
which the recombinant protein is expressed with an
antigenic amino acid sequence at one of its ends, to
which commercial antibodies are readily available,