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of external signals, including hormones and other ligands, and sites for
the recognition and attachment of other cells. Internally, plasma membranes can act as points of attachment for intracellular structures, in
particular those concerned with cell motility and other cytoskeletal
functions. Cell membranes are synthesized by the rough endoplasmic
reticulum in conjunction with the Golgi apparatus.
###### Cell coat (glycocalyx)
The external surface of a plasma membrane differs structurally from
internal membranes in that it possesses an external, fuzzy, carbohydraterich coat, the glycocalyx. The cell coat forms an integral part of the
plasma membrane, projecting as a diffusely filamentous layer 2–20 nm
or more from the lipoprotein surface. The cell coat is composed of the
carbohydrate portions of glycoproteins and glycolipids embedded in
the plasma membrane (see Fig. 1.3).
The precise composition of the glycocalyx varies with cell type; many
tissue- and cell type-specific antigens are located in the coat, including
the major histocompatibility complex of the immune system and, in
the case of erythrocytes, blood group antigens. Therefore, the glycocalyx
plays a significant role in organ transplant compatibility. The glycocalyx
found on apical microvilli of enterocytes, the cells forming the lining
epithelium of the intestine, consists of enzymes involved in the digestive process. Intestinal microvilli are cylindrical projections (1–2 µm
long and about 0.1 µm in diameter) forming a closely packed layer
called the brush border that increases the absorptive function of
enterocytes.
###### Cytoplasm
###### Compartments and functional organization
The cytoplasm consists of the cytosol, a gel-like material enclosed by
the cell or plasma membrane. The cytosol is made up of colloidal proteins such as enzymes, carbohydrates and small protein molecules,
together with ribosomes and ribonucleic acids. The cytoplasm contains
two cytomembrane systems, the endoplasmic reticulum and Golgi
apparatus, as well as membrane-bound organelles (lysosomes, peroxisomes and mitochondria), membrane-free inclusions (lipid droplets,
glycogen and pigments) and the cytoskeleton. The nuclear contents,
the nucleoplasm, are separated from the cytoplasm by the nuclear
envelope.
###### Endoplasmic reticulum
The endoplasmic reticulum is a system of interconnecting membranelined channels within the cytoplasm (Fig. 1.4). These channels take
various forms, including cisternae (flattened sacs), tubules and vesicles.
The membranes divide the cytoplasm into two major compartments.
The intramembranous compartment, or cisternal space, is where secretory products are stored or transported to the Golgi complex and cell
exterior. The cisternal space is continuous with the perinuclear space.
Structurally, the channel system can be divided into rough or granu
lar endoplasmic reticulum (RER), which has ribosomes attached to its
outer, cytosolic surface, and smooth or agranular endoplasmic reticulum (SER), which lacks ribosomes. The functions of the endoplasmic
reticulum vary greatly and include: the synthesis, folding and transport
of proteins; synthesis and transport of phospholipids and steroids; and
storage of calcium within the cisternal space and regulated release into
the cytoplasm. In general, RER is well developed in cells that produce
**Fig 1 4 Smooth endoplasmic reticulum with associated vesicles The**
abundant proteins; SER is abundant in steroid-producing cells and
muscle cells. A variant of the endoplasmic reticulum in muscle cells is
the sarcoplasmic reticulum, involved in calcium storage and release for
muscle contraction. For further reading on the endoplasmic reticulum,
see Bravo et al (2013).
###### Smooth endoplasmic reticulum
The smooth endoplasmic reticulum (see Fig. 1.4) is associated with
carbohydrate metabolism and many other metabolic processes, including detoxification and synthesis of lipids, cholesterol and steroids. The
membranes of the smooth endoplasmic reticulum serve as surfaces for
the attachment of many enzyme systems, e.g. the enzyme cytochrome
P450, which is involved in important detoxification mechanisms and
is thus accessible to its substrates, which are generally lipophilic. The
membranes also cooperate with the rough endoplasmic reticulum
and the Golgi apparatus to synthesize new membranes; the protein,
carbohydrate and lipid components are added in different structural
compartments. The smooth endoplasmic reticulum in hepatocytes contains the enzyme glucose-6-phosphatase, which converts glucose-6phosphate to glucose, a step in gluconeogenesis.
###### Rough endoplasmic reticulum
The rough endoplasmic reticulum is a site of protein synthesis; its
cytosolic surface is studded with ribosomes (Fig. 1.5E). Ribosomes only
bind to the endoplasmic reticulum when proteins targeted for secretion
begin to be synthesized. Most proteins pass through its membranes and
accumulate within its cisternae, although some integral membrane proteins, e.g. plasma membrane receptors, are inserted into the rough
endoplasmic reticulum membrane, where they remain. After passage
from the rough endoplasmic reticulum, proteins remain in membranebound cytoplasmic organelles such as lysosomes, become incorporated
into new plasma membrane, or are secreted by the cell. Some carbohydrates are also synthesized by enzymes within the cavities of the rough
endoplasmic reticulum and may be attached to newly formed protein
(glycosylation). Vesicles are budded off from the rough endoplasmic
reticulum for transport to the Golgi as part of the protein-targeting
mechanism of the cell.
###### Ribosomes, polyribosomes and protein synthesis
Ribosomes are macromolecular machines that catalyse the synthesis of
proteins from amino acids; synthesis and assembly into subunits takes
place in the nucleolus and includes the association of ribosomal RNA
(rRNA) with ribosomal proteins translocated from their site of synthesis
in the cytoplasm. The individual subunits are then transported into the
cytoplasm, where they remain separate from each other when not
actively synthesizing proteins. Ribosomes are granules approximately
25 nm in diameter, composed of rRNA molecules and proteins assembled into two unequal subunits. The subunits can be separated by their
sedimentation coefficients (S) in an ultracentrifuge into larger 60S and
smaller 40S components. These are associated with 73 different proteins (40 in the large subunit and 33 in the small), which have structural
and enzymatic functions. Three small, highly convoluted rRNA strands
(28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is
in the small subunit.
A typical cell contains millions of ribosomes. They may form groups
(polyribosomes or polysomes) attached to messenger RNA (mRNA),
which they translate during protein synthesis for use outside the system
of membrane compartments, e.g. enzymes of the cytosol and cytoskeletal proteins. Some of the cytosolic products include proteins that can
be inserted directly into (or through) membranes of selected organelles,
such as mitochondria and peroxisomes. Ribosomes may be attached to
the membranes of the rough endoplasmic reticulum (see Fig. 1.5E).
In a mature polyribosome, all the attachment sites of the mRNA are
occupied as ribosomes move along it, synthesizing protein according
to its nucleotide sequence. Consequently, the number and spacing of
ribosomes in a polyribosome indicate the length of the mRNA molecule and hence the size of the protein being made. The two subunits
have separate roles in protein synthesis. The 40S subunit is the site of
attachment and translation of mRNA. The 60S subunit is responsible
for the release of the new protein and, where appropriate, attachment
to the endoplasmic reticulum via an intermediate docking protein that
directs the newly synthesized protein through the membrane into the
cisternal space.
###### Golgi apparatus (Golgi complex)
The Golgi apparatus is a distinct cytomembrane system located near the
-----
| 34 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PyMuPDF4LLMTextLoader |
###### CHAPTER
Basic structure and function of cells
##### 1
###### CELL STRUCTURE
###### GENERAL CHARACTERISTICS OF CELLS
The shapes of mammalian cells vary widely depending on their interactions with each other, their extracellular environment and internal
structures. Their surfaces are often highly folded when absorptive or
transport functions take place across their boundaries. Cell size is
limited by rates of diffusion, either that of material entering or leaving
cells, or that of diffusion within them. Movement of macromolecules
can be much accelerated and also directed by processes of active transport across the plasma membrane and by transport mechanisms within
the cell. According to the location of absorptive or transport functions,
apical microvilli (Fig. 1.1) or basolateral infoldings create a large
surface area for transport or diffusion.
Motility is a characteristic of most cells, in the form of movements
of cytoplasm or specific organelles from one part of the cell to another.
It also includes: the extension of parts of the cell surface such as pseudopodia, lamellipodia, filopodia and microvilli; locomotion of entire
cells, as in the amoeboid migration of tissue macrophages; the beating
of flagella or cilia to move the cell (e.g. in spermatozoa) or fluids overlying it (e.g. in respiratory epithelium); cell division; and muscle contraction. Cell movements are also involved in the uptake of materials from
their environment (endocytosis, phagocytosis) and the passage of large
molecular complexes out of cells (exocytosis, secretion).
Epithelial cells rarely operate independently of each other and com
monly form aggregates by adhesion, often assisted by specialized intercellular junctions. They may also communicate with each other either
by generating and detecting molecular signals that diffuse across intercellular spaces, or more rapidly by generating interactions between
membrane-bound signalling molecules. Cohesive groups of cells constitute tissues, and more complex assemblies of tissues form functional
systems or organs.
Most cells are between 5 and 50 µm in diameter: e.g. resting lym
phocytes are 6 µm across, red blood cells 7.5 µm and columnar epithelial cells 20 µm tall and 10 µm wide (all measurements are approximate).
Some cells are much larger than this: e.g. megakaryocytes of the bone
marrow and osteoclasts of the remodelling bone are more than 200 µm
in diameter. Neurones and skeletal muscle cells have relatively extended
shapes, some of the former being over 1 m in length.
###### CELLULAR ORGANIZATION
Each cell is contained within its limiting plasma membrane, which
encloses the cytoplasm. All cells, except mature red blood cells, also
contain a nucleus that is surrounded by a nuclear membrane or envelope (see Fig. 1.1; **Fig. 1.2). The nucleus includes: the genome of the**
cell contained within the chromosomes; the nucleolus; and other subnuclear structures. The cytoplasm contains cytomembranes and several
membrane-bound structures, called organelles, which form separate
Mitochondrion
Surface projections
(cilia, microvilli)
Surface invagination
Actin filaments
Vesicle
Cell junctions
Desmosome
Plasma membrane
Peroxisomes
Cytosol
Nuclear pore
Intermediate
filaments
Smooth endoplasmic
reticulum
Nuclear envelope
Nucleus
Rough endoplasmic
reticulum
Golgi apparatus
Nucleolus
Ribosome
Microtubules
Centriole pair
Lysosomes
Cell surface folds
-----
| 31 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PyMuPDF4LLMTextLoader |
Combinations of biochemical, biophysical and biological tech
niques have revealed that lipids are not homogenously distributed in
membranes, but that some are organized into microdomains in the
bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in
sphingomyelin and cholesterol. The ability of select subsets of proteins
to partition into different lipid microdomains has profound effects on
their function, e.g. in T-cell receptor and cell–cell signalling. The highly
organized environment of the domains provides a signalling, trafficking
and membrane fusion environment.
-----
| 33 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PyMuPDF4LLMTextLoader |
The glycocalyx plays a significant role in maintenance of the integrity
of tissues and in a wide range of dynamic cellular processes, e.g. serving
as a vascular permeability barrier and transducing fluid shear stress to
the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of
the glycocalyx on the endothelial surface of large blood vessels precedes
inflammation, a conditioning factor of atheromatosis (e.g. deposits of
cholesterol in the vascular wall leading to partial or complete obstruction of the vascular lumen).
Protein synthesis on ribosomes may be suppressed by a class of RNA
molecules known as small interfering RNA (siRNA) or silencing RNA.
These molecules are typically 20–25 nucleotides in length and bind (as
a complex with proteins) to specific mRNA molecules via their complementary sequence. This triggers the enzymatic destruction of the mRNA
or prevents the movement of ribosomes along it. Synthesis of the
encoded protein is thus prevented. Their normal function may have
antiviral or other protective effects; there is also potential for developing
artificial siRNAs as a therapeutic tool for silencing disease-related genes.
-----
| 35 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PyMuPDF4LLMTextLoader |
External
(extracellular)
surface
Internal
(intracellular)
surface
CC MVMV APMAPM
AJCAJC
MM
MM
CyCy
LPMLPM
NN
ENEN
**Fig. 1.2 The structural organization and some principal organelles of a**
typical cell. This example is a ciliated columnar epithelial cell from human
nasal mucosa. The central cell, which occupies most of the field of
view, is closely apposed to its neighbours along their lateral plasma
membranes. Within the apical junctional complex, these membranes form
a tightly sealed zone (tight junction) that isolates underlying tissues from,
in this instance, the nasal cavity. Abbreviations: AJC, apical junctional
complex; APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN,
euchromatic nucleus; LPM, lateral plasma membrane; M, mitochondria;
MV, microvilli; N, nucleolus. (Courtesy of Dr Bart Wagner, Histopathology
Department, Sheffield Teaching Hospitals, UK.)
and distinct compartments within the cytoplasm. Cytomembranes
include the rough and smooth endoplasmic reticulum and Golgi apparatus, as well as vesicles derived from them. Organelles include lysosomes, peroxisomes and mitochondria. The nucleus and mitochondria
are enclosed by a double-membrane system; lysosomes and peroxisomes have a single bounding membrane. There are also nonmembranous structures, called inclusions, which lie free in the cytosolic
compartment. They include lipid droplets, glycogen aggregates and pigments (e.g. lipofuscin). In addition, ribosomes and several filamentous
protein networks, known collectively as the cytoskeleton, are found in
the cytosol. The cytoskeleton determines general cell shape and supports specialized extensions of the cell surface (microvilli, cilia, flagella). It is involved in the assembly of specific structures (e.g. centrioles)
and controls cargo transport in the cytoplasm. The cytosol contains
many soluble proteins, ions and metabolites.
###### Plasma membrane
Cells are enclosed by a distinct plasma membrane, which shares features with the cytomembrane system that compartmentalizes the cytoplasm and surrounds the nucleus. All membranes are composed of
lipids (mainly phospholipids, cholesterol and glycolipids) and proteins, in approximately equal ratios. Plasma membrane lipids form a
lipid bilayer, a layer two molecules thick. The hydrophobic ends of each
lipid molecule face the interior of the membrane and the hydrophilic
ends face outwards. Most proteins are embedded within, or float in, the
lipid bilayer as a fluid mosaic. Some proteins, because of extensive
hydrophobic regions of their polypeptide chains, span the entire width
of the membrane (transmembrane proteins), whereas others are only
superficially attached to the bilayer by lipid groups. Both are integral
(intrinsic) membrane proteins as distinct from peripheral (extrinsic)
**Fig. 1.3 The molecular organization of the plasma membrane, according**
to the fluid mosaic model of membrane structure. Intrinsic or integral
membrane proteins include diffusion or transport channel complexes,
receptor proteins and adhesion molecules. These may span the thickness
of the membrane (transmembrane proteins) and can have both
extracellular and cytoplasmic domains. Transmembrane proteins have
hydrophobic zones, which cross the phospholipid bilayer and allow the
protein to ‘float’ in the plane of the membrane. Some proteins are
restricted in their freedom of movement where their cytoplasmic domains
are tethered to the cytoskeleton.
charides and polysaccharides are bound either to proteins (glycoproteins) or to lipids (glycolipids), and project mainly into the extracellular
domain (Fig. 1.3).
In the electron microscope, membranes fixed and contrasted by
heavy metals such as osmium tetroxide appear in section as two densely
stained layers separated by an electron-translucent zone – the classic
unit membrane. The total thickness of each layer is about 7.5 nm. The
overall thickness of the plasma membrane is typically 15 nm. Freezefracture cleavage planes usually pass along the hydrophobic portion of
the bilayer, where the hydrophobic tails of phospholipids meet, and
split the bilayer into two leaflets. Each cleaved leaflet has a surface and
a face. The surface of each leaflet faces either the extracellular surface
(ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The
extracellular face (EF) and protoplasmic face (PF) of each leaflet are
artificially produced during membrane splitting. This technique has
also demonstrated intramembranous particles embedded in the lipid
bilayer; in most cases, these represent large transmembrane protein
molecules or complexes of proteins. Intramembranous particles are
distributed asymmetrically between the two half-layers, usually adhering more to one half of the bilayer than to the other. In plasma membranes, the intracellular leaflet carries most particles, seen on its face
(the PF). Where they have been identified, clusters of particles usually
represent channels for the transmembrane passage of ions or molecules
between adjacent cells (gap junctions).
Biophysical measurements show the lipid bilayer to be highly fluid,
allowing diffusion in the plane of the membrane. Thus proteins are able
to move freely in such planes unless anchored from within the cell.
Membranes in general, and the plasma membrane in particular, form
boundaries selectively limiting diffusion and creating physiologically
distinct compartments. Lipid bilayers are impermeable to hydrophilic
solutes and ions, and so membranes actively control the passage of ions
and small organic molecules such as nutrients, through the activity of
membrane transport proteins. However, lipid-soluble substances can
pass directly through the membrane so that, for example, steroid hormones enter the cytoplasm freely. Their receptor proteins are either
cytosolic or nuclear, rather than being located on the cell surface.
Plasma membranes are able to generate electrochemical gradients
and potential differences by selective ion transport and actively take up
-----
| 32 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PyMuPDF4LLMTextLoader |
Cell structure
5
1
RETPaHC
CC MMVV AAPPMM
AAJJCC
Receptor
Transmembrane protein
pore complex
of proteins
Carbohydrate
residues
External
(extracellular)
surface
MM
MM
CCyy
LLPPMM
Internal
(intracellular)
surface
NN Lipid bilayer
appearance
in electron
microscope
Intrinsic
membrane
protein Extrinsic Transmembrane
protein
protein Transport Non-polar tail
or diffusion of phospholipid
channel Cytoskeletal
Polar end of
element
EENN phospholipid
Fig . 1 .3 The molecular organization of the plasma membrane, according
to the fluid mosaic model of membrane structure . Intrinsic or integral
membrane proteins include diffusion or transport channel complexes,
receptor proteins and adhesion molecules . These may span the thickness
of the membrane (transmembrane proteins) and can have both
extracellular and cytoplasmic domains . Transmembrane proteins have
hydrophobic zones, which cross the phospholipid bilayer and allow the
Fig . 1 .2 The structural organization and some principal organelles of a
protein to ‘float’ in the plane of the membrane . Some proteins are
typical cell . This example is a ciliated columnar epithelial cell from human
restricted in their freedom of movement where their cytoplasmic domains
nasal mucosa . The central cell, which occupies most of the field of
are tethered to the cytoskeleton .
view, is closely apposed to its neighbours along their lateral plasma
membranes . Within the apical junctional complex, these membranes form
a tightly sealed zone (tight junction) that isolates underlying tissues from,
charides and polysaccharides are bound either to proteins (glycopro-
in this instance, the nasal cavity . Abbreviations: AJC, apical junctional
teins) or to lipids (glycolipids), and project mainly into the extracellular
complex; APM, apical plasma membrane; C, cilia; Cy, cytoplasm; EN,
domain (Fig. 1.3).
euchromatic nucleus; LPM, lateral plasma membrane; M, mitochondria;
In the electron microscope, membranes fixed and contrasted by
MV, microvilli; N, nucleolus . (Courtesy of Dr Bart Wagner, Histopathology
heavy metals such as osmium tetroxide appear in section as two densely
Department, Sheffield Teaching Hospitals, UK .)
stained layers separated by an electron-translucent zone – the classic
unit membrane. The total thickness of each layer is about 7.5 nm. The
and distinct compartments within the cytoplasm. Cytomembranes
overall thickness of the plasma membrane is typically 15 nm. Freeze-
include the rough and smooth endoplasmic reticulum and Golgi appa-
fracture cleavage planes usually pass along the hydrophobic portion of
ratus, as well as vesicles derived from them. Organelles include lyso-
the bilayer, where the hydrophobic tails of phospholipids meet, and
somes, peroxisomes and mitochondria. The nucleus and mitochondria
split the bilayer into two leaflets. Each cleaved leaflet has a surface and
are enclosed by a double-membrane system; lysosomes and peroxi-
a face. The surface of each leaflet faces either the extracellular surface
somes have a single bounding membrane. There are also non-
(ES) or the intracellular or protoplasmic (cytoplasmic) surface (PS). The
membranous structures, called inclusions, which lie free in the cytosolic
extracellular face (EF) and protoplasmic face (PF) of each leaflet are
compartment. They include lipid droplets, glycogen aggregates and pig-
artificially produced during membrane splitting. This technique has
ments (e.g. lipofuscin). In addition, ribosomes and several filamentous
also demonstrated intramembranous particles embedded in the lipid
protein networks, known collectively as the cytoskeleton, are found in
bilayer; in most cases, these represent large transmembrane protein
the cytosol. The cytoskeleton determines general cell shape and sup-
molecules or complexes of proteins. Intramembranous particles are
ports specialized extensions of the cell surface (microvilli, cilia, flag-
distributed asymmetrically between the two half-layers, usually adher-
ella). It is involved in the assembly of specific structures (e.g. centrioles)
ing more to one half of the bilayer than to the other. In plasma mem-
and controls cargo transport in the cytoplasm. The cytosol contains
branes, the intracellular leaflet carries most particles, seen on its face
many soluble proteins, ions and metabolites.
(the PF). Where they have been identified, clusters of particles usually
represent channels for the transmembrane passage of ions or molecules
Plasma membrane
between adjacent cells (gap junctions).
Biophysical measurements show the lipid bilayer to be highly fluid,
Cells are enclosed by a distinct plasma membrane, which shares fea- allowing diffusion in the plane of the membrane. Thus proteins are able
tures with the cytomembrane system that compartmentalizes the cyto- to move freely in such planes unless anchored from within the cell.
plasm and surrounds the nucleus. All membranes are composed of Membranes in general, and the plasma membrane in particular, form
lipids (mainly phospholipids, cholesterol and glycolipids) and pro- boundaries selectively limiting diffusion and creating physiologically
teins, in approximately equal ratios. Plasma membrane lipids form a distinct compartments. Lipid bilayers are impermeable to hydrophilic
lipid bilayer, a layer two molecules thick. The hydrophobic ends of each solutes and ions, and so membranes actively control the passage of ions
lipid molecule face the interior of the membrane and the hydrophilic and small organic molecules such as nutrients, through the activity of
ends face outwards. Most proteins are embedded within, or float in, the membrane transport proteins. However, lipid-soluble substances can
lipid bilayer as a fluid mosaic. Some proteins, because of extensive pass directly through the membrane so that, for example, steroid hor-
hydrophobic regions of their polypeptide chains, span the entire width mones enter the cytoplasm freely. Their receptor proteins are either
of the membrane (transmembrane proteins), whereas others are only cytosolic or nuclear, rather than being located on the cell surface.
superficially attached to the bilayer by lipid groups. Both are integral Plasma membranes are able to generate electrochemical gradients
(intrinsic) membrane proteins, as distinct from peripheral (extrinsic) and potential differences by selective ion transport, and actively take up
membrane proteins, which are membrane-bound only through their or export small molecules by energy-dependent processes. They also
association with other proteins. Carbohydrates in the form of oligosac- provide surfaces for the attachment of enzymes, sites for the receptors | 32 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PDFPlumberTextLoader |
Basic structure and function of cells
5.e1
1
RETPaHC
Combinations of biochemical, biophysical and biological tech-
niques have revealed that lipids are not homogenously distributed in
membranes, but that some are organized into microdomains in the
bilayer, called ‘detergent-resistant membranes’ or lipid ‘rafts’, rich in
sphingomyelin and cholesterol. The ability of select subsets of proteins
to partition into different lipid microdomains has profound effects on
their function, e.g. in T-cell receptor and cell–cell signalling. The highly
organized environment of the domains provides a signalling, trafficking
and membrane fusion environment. | 33 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PDFPlumberTextLoader |
Basic structure and function of cells
6.e1
1
RETPaHC
The glycocalyx plays a significant role in maintenance of the integrity
of tissues and in a wide range of dynamic cellular processes, e.g. serving
as a vascular permeability barrier and transducing fluid shear stress to
the endothelial cell cytoskeleton (Weinbaum et al 2007). Disruption of
the glycocalyx on the endothelial surface of large blood vessels precedes
inflammation, a conditioning factor of atheromatosis (e.g. deposits of
cholesterol in the vascular wall leading to partial or complete obstruc-
tion of the vascular lumen).
Protein synthesis on ribosomes may be suppressed by a class of RNA
molecules known as small interfering RNA (siRNA) or silencing RNA.
These molecules are typically 20–25 nucleotides in length and bind (as
a complex with proteins) to specific mRNA molecules via their comple-
mentary sequence. This triggers the enzymatic destruction of the mRNA
or prevents the movement of ribosomes along it. Synthesis of the
encoded protein is thus prevented. Their normal function may have
antiviral or other protective effects; there is also potential for developing
artificial siRNAs as a therapeutic tool for silencing disease-related genes. | 35 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PDFPlumberTextLoader |
4
1
NOITCES
CHAPTER
1
Basic structure and function of cells
Epithelial cells rarely operate independently of each other and com-
CELL STRUCTURE
monly form aggregates by adhesion, often assisted by specialized inter-
cellular junctions. They may also communicate with each other either
GENERAL CHARACTERISTICS OF CELLS by generating and detecting molecular signals that diffuse across inter-
cellular spaces, or more rapidly by generating interactions between
The shapes of mammalian cells vary widely depending on their interac- membrane-bound signalling molecules. Cohesive groups of cells con-
tions with each other, their extracellular environment and internal stitute tissues, and more complex assemblies of tissues form functional
structures. Their surfaces are often highly folded when absorptive or systems or organs.
transport functions take place across their boundaries. Cell size is Most cells are between 5 and 50 µm in diameter: e.g. resting lym-
limited by rates of diffusion, either that of material entering or leaving phocytes are 6 µm across, red blood cells 7.5 µm and columnar epithe-
cells, or that of diffusion within them. Movement of macromolecules lial cells 20 µm tall and 10 µm wide (all measurements are approximate).
can be much accelerated and also directed by processes of active trans- Some cells are much larger than this: e.g. megakaryocytes of the bone
port across the plasma membrane and by transport mechanisms within marrow and osteoclasts of the remodelling bone are more than 200 µm
the cell. According to the location of absorptive or transport functions, in diameter. Neurones and skeletal muscle cells have relatively extended
apical microvilli (Fig. 1.1) or basolateral infoldings create a large shapes, some of the former being over 1 m in length.
surface area for transport or diffusion.
Motility is a characteristic of most cells, in the form of movements
of cytoplasm or specific organelles from one part of the cell to another. CELLULAR ORGANIZATION
It also includes: the extension of parts of the cell surface such as pseu-
dopodia, lamellipodia, filopodia and microvilli; locomotion of entire Each cell is contained within its limiting plasma membrane, which
cells, as in the amoeboid migration of tissue macrophages; the beating encloses the cytoplasm. All cells, except mature red blood cells, also
of flagella or cilia to move the cell (e.g. in spermatozoa) or fluids overly- contain a nucleus that is surrounded by a nuclear membrane or enve-
ing it (e.g. in respiratory epithelium); cell division; and muscle contrac- lope (see Fig. 1.1; Fig. 1.2). The nucleus includes: the genome of the
tion. Cell movements are also involved in the uptake of materials from cell contained within the chromosomes; the nucleolus; and other sub-
their environment (endocytosis, phagocytosis) and the passage of large nuclear structures. The cytoplasm contains cytomembranes and several
molecular complexes out of cells (exocytosis, secretion). membrane-bound structures, called organelles, which form separate
Surface projections
(cilia, microvilli)
Surface invagination
Actin filaments
Vesicle Mitochondrion
Cell junctions
Plasma membrane
Desmosome Peroxisomes
Cytosol
Nuclear pore
Intermediate
filaments Nuclear envelope
Smooth endoplasmic Nucleus
reticulum
Nucleolus
Ribosome
Rough endoplasmic
reticulum
Microtubules
Golgi apparatus Centriole pair
Lysosomes
Cell surface folds
Fig . 1 .1 The main structural components and internal organization of a generalized cell . | 31 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PDFPlumberTextLoader |
BaSIC STRuCTuRE aNd fuNCTION Of CEllS
6
1
NOITCES
of external signals, including hormones and other ligands, and sites for abundant proteins; SER is abundant in steroid-producing cells and
the recognition and attachment of other cells. Internally, plasma mem- muscle cells. A variant of the endoplasmic reticulum in muscle cells is
branes can act as points of attachment for intracellular structures, in the sarcoplasmic reticulum, involved in calcium storage and release for
particular those concerned with cell motility and other cytoskeletal muscle contraction. For further reading on the endoplasmic reticulum,
functions. Cell membranes are synthesized by the rough endoplasmic see Bravo et al (2013).
reticulum in conjunction with the Golgi apparatus.
Smooth endoplasmic reticulum
Cell coat (glycocalyx)
The smooth endoplasmic reticulum (see Fig. 1.4) is associated with
The external surface of a plasma membrane differs structurally from carbohydrate metabolism and many other metabolic processes, includ-
internal membranes in that it possesses an external, fuzzy, carbohydrate- ing detoxification and synthesis of lipids, cholesterol and steroids. The
rich coat, the glycocalyx. The cell coat forms an integral part of the membranes of the smooth endoplasmic reticulum serve as surfaces for
plasma membrane, projecting as a diffusely filamentous layer 2–20 nm the attachment of many enzyme systems, e.g. the enzyme cytochrome
or more from the lipoprotein surface. The cell coat is composed of the P450, which is involved in important detoxification mechanisms and
carbohydrate portions of glycoproteins and glycolipids embedded in is thus accessible to its substrates, which are generally lipophilic. The
the plasma membrane (see Fig. 1.3). membranes also cooperate with the rough endoplasmic reticulum
The precise composition of the glycocalyx varies with cell type; many and the Golgi apparatus to synthesize new membranes; the protein,
tissue- and cell type-specific antigens are located in the coat, including carbohydrate and lipid components are added in different structural
the major histocompatibility complex of the immune system and, in compartments. The smooth endoplasmic reticulum in hepatocytes con-
the case of erythrocytes, blood group antigens. Therefore, the glycocalyx tains the enzyme glucose-6-phosphatase, which converts glucose-6-
plays a significant role in organ transplant compatibility. The glycocalyx phosphate to glucose, a step in gluconeogenesis.
found on apical microvilli of enterocytes, the cells forming the lining
epithelium of the intestine, consists of enzymes involved in the diges- Rough endoplasmic reticulum
tive process. Intestinal microvilli are cylindrical projections (1–2 µm The rough endoplasmic reticulum is a site of protein synthesis; its
long and about 0.1 µm in diameter) forming a closely packed layer cytosolic surface is studded with ribosomes (Fig. 1.5E). Ribosomes only
called the brush border that increases the absorptive function of bind to the endoplasmic reticulum when proteins targeted for secretion
enterocytes. begin to be synthesized. Most proteins pass through its membranes and
accumulate within its cisternae, although some integral membrane pro-
Cytoplasm teins, e.g. plasma membrane receptors, are inserted into the rough
endoplasmic reticulum membrane, where they remain. After passage
Compartments and functional organization from the rough endoplasmic reticulum, proteins remain in membrane-
bound cytoplasmic organelles such as lysosomes, become incorporated
The cytoplasm consists of the cytosol, a gel-like material enclosed by
into new plasma membrane, or are secreted by the cell. Some carbohy-
the cell or plasma membrane. The cytosol is made up of colloidal pro-
drates are also synthesized by enzymes within the cavities of the rough
teins such as enzymes, carbohydrates and small protein molecules,
endoplasmic reticulum and may be attached to newly formed protein
together with ribosomes and ribonucleic acids. The cytoplasm contains
(glycosylation). Vesicles are budded off from the rough endoplasmic
two cytomembrane systems, the endoplasmic reticulum and Golgi
reticulum for transport to the Golgi as part of the protein-targeting
apparatus, as well as membrane-bound organelles (lysosomes, peroxi-
mechanism of the cell.
somes and mitochondria), membrane-free inclusions (lipid droplets,
glycogen and pigments) and the cytoskeleton. The nuclear contents, Ribosomes, polyribosomes
the nucleoplasm, are separated from the cytoplasm by the nuclear
and protein synthesis
envelope.
Ribosomes are macromolecular machines that catalyse the synthesis of
Endoplasmic reticulum proteins from amino acids; synthesis and assembly into subunits takes
The endoplasmic reticulum is a system of interconnecting membrane- place in the nucleolus and includes the association of ribosomal RNA
lined channels within the cytoplasm (Fig. 1.4). These channels take (rRNA) with ribosomal proteins translocated from their site of synthesis
various forms, including cisternae (flattened sacs), tubules and vesicles. in the cytoplasm. The individual subunits are then transported into the
The membranes divide the cytoplasm into two major compartments. cytoplasm, where they remain separate from each other when not
The intramembranous compartment, or cisternal space, is where secre- actively synthesizing proteins. Ribosomes are granules approximately
tory products are stored or transported to the Golgi complex and cell 25 nm in diameter, composed of rRNA molecules and proteins assem-
exterior. The cisternal space is continuous with the perinuclear space. bled into two unequal subunits. The subunits can be separated by their
Structurally, the channel system can be divided into rough or granu- sedimentation coefficients (S) in an ultracentrifuge into larger 60S and
lar endoplasmic reticulum (RER), which has ribosomes attached to its smaller 40S components. These are associated with 73 different pro-
outer, cytosolic surface, and smooth or agranular endoplasmic reticu- teins (40 in the large subunit and 33 in the small), which have structural
lum (SER), which lacks ribosomes. The functions of the endoplasmic and enzymatic functions. Three small, highly convoluted rRNA strands
reticulum vary greatly and include: the synthesis, folding and transport (28S, 5.8S and 5S) make up the large subunit, and one strand (18S) is
of proteins; synthesis and transport of phospholipids and steroids; and in the small subunit.
storage of calcium within the cisternal space and regulated release into A typical cell contains millions of ribosomes. They may form groups
the cytoplasm. In general, RER is well developed in cells that produce (polyribosomes or polysomes) attached to messenger RNA (mRNA),
which they translate during protein synthesis for use outside the system
of membrane compartments, e.g. enzymes of the cytosol and cytoskel-
etal proteins. Some of the cytosolic products include proteins that can
be inserted directly into (or through) membranes of selected organelles,
such as mitochondria and peroxisomes. Ribosomes may be attached to
the membranes of the rough endoplasmic reticulum (see Fig. 1.5E).
In a mature polyribosome, all the attachment sites of the mRNA are
occupied as ribosomes move along it, synthesizing protein according
to its nucleotide sequence. Consequently, the number and spacing of
ribosomes in a polyribosome indicate the length of the mRNA mole-
cule and hence the size of the protein being made. The two subunits
have separate roles in protein synthesis. The 40S subunit is the site of
attachment and translation of mRNA. The 60S subunit is responsible
for the release of the new protein and, where appropriate, attachment
to the endoplasmic reticulum via an intermediate docking protein that
directs the newly synthesized protein through the membrane into the
cisternal space.
Golgi apparatus (Golgi complex)
Fig . 1 .4 Smooth endoplasmic reticulum with associated vesicles . The The Golgi apparatus is a distinct cytomembrane system located near the
dense particles are glycogen granules . (Courtesy of Rose Watson, Cancer nucleus and the centrosome. It is particularly prominent in secretory
Research UK .) cells and can be visualized when stained with silver or other metallic | 34 | Gray's Anatomy | grays_anatomy.pdf | https://archive.org/download/GraysAnatomy41E2015PDF/Grays%20Anatomy-41%20E%20%282015%29%20%5BPDF%5D.pdf | PDFPlumberTextLoader |