CELL

Cells are the basic structural and functional unit of body. Its two major parts are the nucleus and the
cytoplasm. The nucleus is separated from the cytoplasm by a nuclear membrane, and the cytoplasm is
separated from the surrounding fluids by a cell membrane, also called the plasma membrane. The
different substances that make up the cell are collectively called protoplasm. Protoplasm is composed
mainly of five basic substances—water, electrolytes, proteins, lipids, and carbohydrates.

MEMBRANOUS STRUCTURES OF THE CELL

Most organelles of the cell are covered by membranes composed primarily of lipids and proteins.
These membranes include:
The cell membrane, nuclear membrane, membrane of the endoplasmic reticulum, and membranes of
the mitochondria, lysosomes, and Golgi apparatus.
CELL MEMBRANE
COMPOSITION:
● Proteins 55%
● Phospholipids 25%
● Cholesterol 13%
● 4% others
● Carbohydrates 3%
LIPIDS:
i. Hydrophilic, polar heads contains phosphate portion
ii. Non polar, hydrophobic tail in center contains fatty acids
iii. Amphipathic means contains both hydrophilic and hydrophobic in nature
iv. Common lipids are phospholipids (phosphatidylethanolamine, choline, inositol and glycerol),
cholesterol and glycolipids
PROTEINS:
● Constitutes 50-55%
Main types are as follows:
1. Peripheral proteins: located on ICF and ECF and attached to cell membrane by GPI
(glycophosphatidyl inositol (glycosylated phospholipds))
These are further classified into two main types which are as follows:
i. External proteins: act as antigens, enzymes and adhesion molecules.
ii. Internal proteins: act as enzymes, units of ion channel, receptor, transporter, vesicle trafficking
and attach to fibril network inside
2. Integral proteins: act as ion channels, transporters and receptors
3. Lipidated proteins: myristoylated, palmitoylated or prenylated (i.e., attached to geranylgeranyl
or farnesyl groups)
4. Membrane carbohydrates🡪 glycocalyx:
● Gives negative surface charge
● It attaches one cell to other
● Act as receptor for insulin
● Play role in immune reactions
5. Types of membrane proteins:
 * PN hemoglobinuria: It is due to the defect in gene. Reflects hemoglobin in urine at night due to
hemolysis and thrombotic events by immune complements.
ENDOPLASMIC RETICULUM

The endoplasmic reticulum is a network of membrane-enclosed sacs or tubules that extend throughout
the cytoplasm and connect to the nuclear envelope.
STRUCTURE:
Their walls are made up of lipid bilayer membranes that contains large number of proteins. Tubular
network structure is known as cisternae and also has flat vesicular structure in the cytoplasm. The space
inside the vesicle is filled with endoplasmic matrix.

TYPES:
It is basically of two types:
a. Rough endoplasmic
reticulum (RER): It contains large
number of ribosomes attached on its surface.
b. Smooth endoplasmic reticulum (SER): No ribosomes are attached on its surface
Rough ER is continuous with the nuclear membrane and usually is folded into a series of flattened sacs.
The outer surface of rough ER is studded with ribosomes, the sites of protein synthesis. Proteins
synthesized by ribosomes attached to rough ER enter spaces within the ER for processing and sorting. In
some cases, enzymes attach the proteins to carbohydrates to form glycoproteins. In other cases,
enzymes attach the proteins to phospholipids, also synthesized by rough ER. These molecules
(glycoproteins and phospholipids) may be incorporated into the membranes of organelles, inserted into
the plasma membrane, or secreted via exocytosis. Thus rough ER produces secretory proteins,
membrane proteins, and many organellar proteins.
Smooth ER extends from the rough ER to form a network of membrane tubules. Unlike rough ER,
smooth ER does not have ribosomes on the outer surfaces of its membrane. However, smooth ER
contains unique enzymes that make it functionally more diverse than rough ER. Because it lacks
ribosomes.
THE STRUCTURAL AND FUNCTIONAL DIFFERENCES BETWEEN ROUGH AND SMOOTH ER:
smooth ER does not synthesize proteins, but it does synthesize fatty acids and steroids, such as
estrogens and testosterone. In liver cells, enzymes of the smooth ER help release glucose into the
bloodstream and inactivate or detoxify lipid-soluble drugs or potentially harmful substances, such as
alcohol, pesticides, and carcinogens (cancer-causing agents). In liver, kidney, and intestinal cells a
smooth ER enzyme removes the phosphate group from glucose-6-phosphate, which allows the “free”
glucose to enter the bloodstream. In muscle cells, the calcium ions (Ca2+) that trigger contraction are
released from the sarcoplasmic reticulum, a form of smooth ER.
FUNCTIONS:

Endoplasmic reticulum is formed primarily of lipid bilayer membrane, similar to the cell membrane, and
its walls are loaded with protein enzymes that catalyze the synthesis of many substances required by the
cell. Most synthesis begins in the endoplasmic reticulum. The products formed there are then passed on
to the Golgi apparatus, where they are further processed before being released into the cytoplasm. It
helps in transport of substance from one side of cell to other side. The important functions of
endoplasmic reticulum are explained as follows:
 1. Proteins Synthesis by the Rough Endoplasmic Reticulum. The rough endoplasmic reticulum is
characterized by large numbers of ribosomes attached to the outer surfaces of the endoplasmic
reticulum membrane. The protein molecules are synthesized within the structures of the
ribosomes. The ribosomes extrude some of the synthesized protein molecules directly into the
cytosol, but they also extrude many more through the wall of the endoplasmic reticulum to the
interior of the endoplasmic vesicles and tubules into the endoplasmic matrix.
2. Lipid Synthesis by the Smooth Endoplasmic Reticulum.
The endoplasmic reticulum also synthesizes lipids, especially phospholipids and cholesterol. These lipids
are rapidly incorporated into the lipid bilayer of the endoplasmic reticulum, thus causing the
endoplasmic reticulum to grow more extensive. This process occurs mainly in the smooth portion of the
endoplasmic reticulum. To keep the endoplasmic reticulum from growing beyond the needs of the cell,
small vesicles called ER vesicles or transport vesicles continually break away from the smooth reticulum;
most of these vesicles then migrate rapidly to the Golgi apparatus.
Other Functions of the Endoplasmic Reticulum.
Other significant functions of the endoplasmic reticulum, especially the smooth reticulum, include the
following:
1. It provides the enzymes that control glycogen breakdown when glycogen is to be used for energy.
2. It provides a vast number of enzymes that are capable of detoxifying substances, such as drugs, that
might damage the cell. It achieves detoxification by processes such as coagulation, oxidation, hydrolysis,
and conjugation with glycuronic acid.

CLINICAL CORRELATION----- SMOOTH ER AND DRUG TOLERANCE:

One of the functions of smooth ER, as noted earlier, is to detoxify certain drugs. Individuals who
repeatedly take such drugs, such as the sedative phenobarbital, develop changes in the smooth ER in
their liver cells. Prolonged administration of phenobarbital results in increased tolerance to the drug;
the same dose no longer produces the same degree of sedation. With repeated exposure to the drug,
the amount of smooth ER and its enzymes increases to protect the cell from its toxic effects. As the
amount of smooth ER increases, higher and higher dosages of the drug are needed to achieve the
original effect. This could result in an increased possibility of overdose and increased drug dependence.

GOLGI APPARATUS

The Golgi apparatus consists of a series of hollow curved sacs called cisternae stacked on top of one
another and surrounded by vesicles. The Golgi apparatus participates in protein modification and
packaging.

FUNCTIONS:

⮚ They provide additional processing of substances already formed by endoplasmic reticulum.

⮚ They also synthesize certain carbohydrates like large polysaccharides e.g. hyaluronic acid
and chondroitin sulfate as:
i. They are major component of proteoglycans and other glandular secretions
ii. They are principal component of organic matrix in bone and cartilage
iii. They are important in cell activities e.g. migration and proliferation.

PROCESSING BY GOLGI APPARATUS:

Golgi apparatus is polarized structure with two distinct sides cis and trans. The cis face is
near the endoplasmic reticulum while the trans face is near the plasma membrane. The membranous
vesicles bud off from rough endoplasmic reticulum and fuse with the cis end of Golgi apparatus. Golgi
vesicles pass to lysosomes and cell exterior by exocytosis. Conversely vesicles are pinched off from the
cell membrane by endocytosis and pass to endosome. From there ,they are recycled.
Vesicular traffic in Golgi apparatus is controlled by various mechanism. One prominent feature is the
involvement of a series of a regulatory proteins controlled by GTP or GDP binging (small G proteins)
associated with vesicles assembly and delivery.
A second prominent feature is the presence of proteins called SNARES ( for soluble N ethylmaleimide
sensitive factor attachment ) .The v (for vesicle) SNAREs on vesicle membrane interact in lock and key
fashion with t (for target)SNAREs.
How do the entry and exit faces differ in function?

Different enzymes in the entry, medial, and exit cisternae of the Golgi complex permit each of these
areas to modify, sort, and package proteins into vesicles for transport to different destinations. The
entry face receives and modifies proteins produced by the rough ER. The medial cisternae add
carbohydrates to proteins to form glycoproteins and lipids to proteins to form lipoproteins. The exit face
modifies the molecules further and then sorts and packages them for transport to their destinations.
Proteins arriving at, passing through, and exiting the Golgi complex do so through maturation of the
cisternae and exchanges that occur via transfer vesicles (Figure):
1. Proteins synthesized by ribosomes on the rough ER are surrounded by a piece of the ER
membrane, which eventually buds from the membrane surface to form transport vesicles.
2. Transport vesicles move toward the entry face of the Golgi complex.
 3. Fusion of several transport vesicles creates the entry face of the Golgi complex and releases
proteins into its lumen (space).
4. The proteins move from the entry face into one or more medial cisternae. Enzymes in the
medial cisternae modify the proteins to form glycoproteins, glycolipids, and lipoproteins.
Transfer vesicles that bud from the edges of the cisternae move specific enzymes back toward
the entry face and move some partially modified proteins toward the exit face.
5. The products of the medial cisternae move into the lumen of the exit face.
6. Within the exit face cisterna, the products are further modified and are sorted and packaged.
7. Some of the processed proteins leave the exit face and are stored in secretory vesicles. These
vesicles deliver the proteins to the plasma membrane, where they are discharged by exocytosis
into the extracellular fluid. For example, certain pancreatic cells release the hormone insulin in
this way.
8. Other processed proteins leave the exit face in membrane vesicles that deliver their contents to
the plasma membrane for incorporation into the membrane. In doing so, the Golgi complex
adds new segments of plasma membrane as existing segments are lost and modifies the number
and distribution of membrane molecules.
9. Finally, some processed proteins leave the exit face in transport vesicles that will carry the
proteins to another cellular destination.

LYSOSOMES

Lysosomes derived from 2 words: lyso means dissolving; -somes means bodies
These are membrane-enclosed vesicles that form from the Golgi complex. These contain as many as 60
kinds of powerful digestive and hydrolytic enzymes that helps in endocytosis. They work best at acidic
pH (the lysosomal interior has a pH of 5, which is 100 times more acidic than the pH of the cytosol (pH
7).
Lysosomal membrane contains 2 important components:
● Active transport pumps that import hydrogen ions (H+).
● Transporters that move the final products of digestion, such as glucose, fatty acids, and amino
acids, into the cytosol.
FUNCTIONS OF LYSOSOMES
• Digest substances that enter a cell via endocytosis and transport final products of digestion into
cytosol.
• Carry out autophagy, the digestion of worn-out organelles.
• Implement autolysis, the digestion of an entire cell.
• Accomplish extracellular digestion.
ENDOCYTOSIS BY LYSOSOMES:
⮚ Molecules are taken up from outside the cell in endocytic vesicles, which fuse with early
endosomes. Membrane components are recycled as the early endosomes mature into late
endosomes.
⮚ Transport vesicles carrying acid hydrolases from the Golgi apparatus then fuse with late
endosomes, which mature into lysosomes as they acquire a full complement of
lysosomal enzymes.
⮚ The acid hydrolases dissociate from the mannose-6-phosphate receptor when the transport
vesicles fuse with late endosomes, and the receptors are recycled to the Golgi apparatus.
⮚ Molecules are taken up from outside the cell in endocytic vesicles, which fuse with early
endosomes.
⮚ Membrane components are recycled as the early endosomes mature into late endosomes.
⮚ Transport vesicles carrying acid hydrolases from the Golgi apparatus then fuse with late
endosomes, which mature into lysosomes as they acquire a full complement of lysosomal
enzymes.
⮚ The acid hydrolases dissociate from the mannose-6-phosphate receptor when the transport
vesicles fuse with late endosomes, and the receptors are recycled to the Golgi apparatus.
PHAGOCYTOSIS AND AUTOLYSIS BY LYSOSOMES:

In addition to degrading molecules taken up by endocytosis, lysosomes digest material derived from two
other routes: phagocytosis and autophagy.
In phagocytosis, specialized cells, such as macrophages, take up and degrade large particles, including
bacteria, cell debris, and aged cells that need to be eliminated from the body. Such large particles are
taken up in phagocytic vacuoles (phagosomes), which then fuse with lysosomes, resulting in digestion of
their contents. The lysosomes formed in this way (phagolysosomes) can be quite large and
heterogeneous, since their size and shape is determined by the content of material that is being
digested.
Lysosomes are also responsible for autophagy, the gradual turnover of the cell’s own components. The
first step of autophagy appears to be the enclosure of an organelle (e.g., a mitochondrion) in membrane
derived from the ER. The resulting vesicle (an autophagosome) then fuses with a lysosome, and its
contents are digested. Autophagy is responsible for the gradual turnover of cytoplasmic organelles.

CLINICAL SIGNIFICANCE
When a lysosomal enzyme is congenitally absent, the lysosomes become engorged with the material the
enzyme normally degrades. This eventually leads to one of the lysosomal diseases (also called lysosomal
storage diseases).
Over 50 such diseases have been recognized
Most common are:
o Fabry disease (deficiency of α-galactosidase)
o Gaucher disease (deficiency in β-galactocerebrosidase)
o Tay-Sachs disease (by the loss of hexosaminidase A)
 PEROXISOMES

Similar in structure to lysosomes but smaller, 0.5 μm in diameter.

Peroxisomes are also called microbodies. These are different in 2 important ways:
⮚ They are believed to be formed by self replication (or perhaps by budding off from SER rather
than Golgi apparatus)
⮚ They contain oxidases rather than hydrolases.
These are most abundantly present in the liver where play their role in the detoxification like that of
alcohol.
Oxidation- reduction reaction produces H2O2 by the action of oxidases. This H2O2 is a potentially toxic
compound, and associated free radicals. However, peroxisomes also contain the enzyme catalase,
which decomposes H2O2. as superoxide.

CLINICAL SIGNIFICANCE
Protect the parts of the cell from toxic effects of H2O2 as production and degradation of H2O2 occur
within the same organelle.
Without peroxisomes, byproducts of metabolism could accumulate inside a cell and result in cellular
death.
The enzyme catalase produces the following reaction:
2H 2 O 2 → 2 H 2 O + O 2 .
Catalase is one of the fastest acting enzymes known and it is this reaction that produces the
characteristic fizzing when hydrogen peroxide is poured on a wound.

MITOCHONDRIA
Mitochondria are known as the power houses of the cell. All cells in the body, with the exception of
mature red blood cells, have from a hundred to a few thousand mitochondria.
STRUCTURE:

These vary in size and shape. It is a double membrane bounded organelle, separated by a
narrow intermembranous space.
⮚ Inner membrane 🡪 has many folds called cristae
⮚ Outer membrane 🡪 is smooth , contains integral proteins called porins for free diffusion of
molecules across the membranes
⮚ Central matrix space--- contains enzymes to extract energy from nutrients

MITOCHONDRIAL GENOME
⮚ Mitochondria are self-replicative, which means that one mitochondrion can form a second one,
a third one, and so on whenever the cell needs increased amounts of ATP. Indeed, the
mitochondria contain DNA similar to that found in the cell nucleus. Mitochondrial DNA is more
primitive (consisting of a circular, relatively small, double stranded molecule) than that found
within the cell nucleus. The DNA of the mitochondrion plays a similar role, controlling replication
of the mitochondrion. Cells that are faced with increased energy demands—for example, in
skeletal muscles subjected to chronic exercise training—may increase the density of
mitochondria to supply the additional energy required

All of the mitochondria in a person’s body are derived from those inherited from the mother’s
fertilized egg cell.
FUNCTIONS
⮚ Generate ATP through reactions of aerobic cellular respiration.

⮚ Mitochondria also play an important and early role in apoptosis, the orderly, genetically
programmed death of a cell. In response to stimuli such as large numbers of destructive free
radicals, DNA damage, growth factor deprivation, or lack of oxygen and nutrients, certain
chemicals are released from mitochondria following the formation of a pore in the outer
mitochondrial membrane. One of the chemicals released into the cytosol of the cell is
cytochrome c, which while inside the mitochondria is involved in aerobic cellular respiration. In
the cytosol, however, cytochrome c and other substances initiate a cascade of activation of
protein-digesting enzymes that bring about apoptosis.

CLINICAL SIGNIFICANCE
⮚ Mitochondria produce superoxide radicals🡪 oxidative stress
⮚ Accumulations in mutations in mitochondrial DNA may lead to aging
⮚ Mutations in mitochondrial DNA occur ten times faster than nuclear DNA
⮚ These mutations lead to mitochondrial diseases

NUCLEUS

The nucleus is the control center of the cell and sends messages to the cell to grow and mature,
replicate, or die. The nucleus is the organelle that contains the DNA of a cell. A gene is a length
of DNA that codes for the production of a specific polypeptide chain. In order for genes to be
expressed, they must first direct the production of complementary RNA molecules. That process
is called genetic transcription.
STRUCTURE:
 ⮚ Spherical or oval shaped structure usually located near the center of the cell
⮚ The nucleus consists of:
▪ Nuclear envelope also called as nuclear membrane
▪ Nucleoplasm that also forms nuclear matrix
▪ Nucleoli

▪ The nuclear membrane, also called the nuclear envelope, is actually two separate bilayer
membranes, one inside the other. The outer membrane is continuous with the endoplasmic
reticulum of the cell cytoplasm, and the space between the two nuclear membranes is also
continuous with the space inside the endoplasmic reticulum.
▪ The nuclear membrane is penetrated by several thousand nuclear pores that allow
necessary traffic to move between the nucleus and the cytoplasm.
▪ The nucleoli are highly staining structures, which are simply an accumulation of large
amounts of RNA and proteins of the types found in ribosomes. The nucleolus enlarges
considerably when the cell is actively synthesizing proteins.
NUCLEOLI AND FORMATION OF RIBOSOMES
The nuclei of most cells contain one or more highly staining structures called nucleoli. The nucleolus,
unlike most other organelles, does not have a limiting membrane. Instead, it is simply an accumulation
of large amounts of RNA and proteins of the types found in ribosomes. The nucleolus enlarges
considerably when the cell is actively synthesizing proteins.
Formation of the nucleoli (and of the ribosomes in the cytoplasm outside the nucleus) begins in the
nucleus.
⮚ First, specific DNA genes in the chromosomes cause RNA to be synthesized.
⮚ Some of this synthesized RNA is stored in the nucleoli, but most of it is transported outward
through the nuclear pores into the cytoplasm.
⮚ Here it is used in conjunction with specific proteins to assemble “mature” ribosomes that play
an essential role in forming cytoplasmic proteins.

FUNCTIONS OF NUCLEUS
1. Controls cellular structure.
2. Directs cellular activities.
3. Produces ribosomes in nucleoli.

CYTOSKELETON
FILAMENT AND TUBULAR STRUCTURES
The cell cytoskeleton is a network of fibrillar proteins organized into filaments or tubules. It originates
as precursor proteins synthesized by ribosomes in the cytoplasm. It originates as precursor proteins
synthesized by ribosomes in the cytoplasm.
It is made primarily of the following along with proteins that anchor and tie them together
 a) Microtubules
b) Intermediate filaments
c) Microfilaments

a) MICROTUBULES
The microtubules are non-branching, rigid, hollow tubes of various length. It is a network of various
proteins which can quickly disassemble in one location and reassemble in another. The outer diameter
of a microtubule measures about 25 nm, whereas its luminal diameter is about 15 nm.
They are made up of two globular protein subunits:
α- and β- tubulin. A third subunit, ϒ-tubulin, is associated with the production of microtubules by
centrosomes.
The α- and β- subunits form heterodimers, which aggregate to form long tubes made up of stacked
rings, with each ring usually containing 13 subunits.

MTOC (MICROTUBULE ORGANIZING CENTER)

❑ A structure inside the cell from where microtubules organize following depolymerization to turn
into tubular structures arranged in distinct pattern and number.
(This polymerization requires the presence of Magnesium ions and guanosine triphosphate (GTP).)
❑ 2 IMPORTANT FUNCTIONS:
1. To determine the organization of eukaryotic flagella and cilia
2. To organize the spindle apparatus necessary in the pulling of chromosomes toward opposite
sides during mitosis and meiosis.
WHAT IS THE ROLE OF MAPs?
In the intracellular transport of organelles and vesicles, special MAPs called motor proteins play an
important role. These proteins become attached to the organelles (or vesicles) and then move along
the microtubule track to transport the organelle to the required destination. The motor proteins
possess ATPase activity and are capable of hydrolyzing ATP to produce the energy needed for
intracellular movement of organelles and vesicles.

Two families of such motor proteins have been identified: kinesins and dyneins.
 ⮚ The kinesins move organelles away from the MTOC toward the plus end of the microtubule,
and thus carry the organelles from the cell center toward the periphery
⮚ The dyneins move the organelles toward the minus end of the microtubules and therefore
transport the organelles from the periphery toward the cell center.

FUNCTIONS:
1. Microtubules provide tracks along which several different molecular motors move
transport vesicles, organelles such as secretory granules and mitochondria from one
part of the cell to another. The microtubule-associated proteins (MAPs) i.e., kinesins
and dyneins play an important role in this transport.
2. They also form the mitotic spindle, which moves the chromosomes in mitosis.
3. The microtubules maintain the cell shape.
4. They form cilia and flagella and impart mobility to these structures.
5. The cytoskeleton performs a very important function in the motile cells of the body
(e.g., the leukocytes and macrophages). In such cells, the bundles of microfilaments
undergo active contraction to produce pseudopodia which enable the cells to move
from one location to another.
CLINICAL SIGNIFICANCE:
Several drugs disrupt cellular function through interaction with microtubules. Microtubules assembly is
prevented by colchicine and vinblastine. The anticancer drug paclitaxel (Taxol) binds to microtubules
and makes them so stable that organelles cannot move. Mitotic spindles cannot form and the cells die.

b) INTERMEDIATE FILAMENTS
The intermediate filaments represent a very heterogeneous group of filaments made up of several
different proteins. They are 8-14 nm in diameter.
TYPES OF INTERMEDIATE FILAMENTS:
The 5 most common varieties are:
TYPES LOCATION FUNCTIONS

KERATIN EPITHELIAL CELLS Stabilization of shape of the cell and strengthen its
attachment to basal lamina and neighboring cells
VIMENTIN CELLS OF Maintain cellular integrity, stabilize cytoskeleton
MESENCHYMAL interactions and provide resistance to avoid cell
ORIGIN damage
DESMIN SMOOTH MUSCLE In smooth muscle cells transmit the pull of contractile
CELLS proteins. In skeletal and cardiac muscle cells link Z
discs of the peripheral myofibrils to the plasma
membrane.
NEUROFILAMENTS NEURONS Provide structural support to the cell body and its
processes.

GLIAL ASTROCYTES Support to the tissue of CNS.

LAMIN NUCLEAR Provide structural support to the nuclear envelope.

LAMINA

CLINICAL SIGNIFICANCE:
As the intermediate filaments provide structural support for the cells, so in their absence the cells
rupture more easily and blistering of skin is more common.
They can also be used as the cellular markers because the proteins that make up these filaments are
cell type specific.
For example , vimentin is a major intermediate filament in fibroblasts, whereas cytokeratin is
expressed in epithelial cells.
c) MICROFILAMENTS:
The microfilaments are also called actin filaments or thin filaments. They are slender, rod shaped
structures, averaging 5-9 nm in diameter. These filaments are comprised of the protein called actin. The
free actin exists as globular monomers called G-actin. The G-actin monomers polymerize in a linear
manner to form actin filaments. Each actin filaments= consists of a double stranded helix filamentous
actin (F-actin).
FUNCTIONS:
🡺 They interact with different types of actin-binding proteins (ABPs). The most commonly
occurring ABP is myosin, but several other ABPs have also been identified. These include
α-actinin, β-spectrin, fimbrin, villin, fascin, gelsolin and adductin.
🡺 In non-muscle cells they contribute to form the structural framework of the cell.
🡺 They also bind to the intrinsic proteins of the cell membrane and serve to anchor these
proteins in position.
🡺 On the epithelial surfaces the microfilaments serve to form the structural core of the
microvilli.
🡺 In motile cells, the microfilaments of the cell cortex play an important role in the cell
migratory activity by forming the primary structural component of the pseudopodial
processes.
CLINICAL SIGNIFICANCE:
These are important in the motility of the cell structures so any abnormality in these may lead to
motility dysfunction of the cells. The proteins constituting microfilaments play an important role in
anchoring the cells so any abnormality in these lead to hereditary disorders (like Hereditary
spherocytosis due to the defect in ankyrin and spectrin).
TERMINAL WEB:
In those epithelial cells that bear microvilli on their free surface, the microfilaments and intermediate
filaments of keratin variety form a transversely arranged network in the most apical cytoplasm; this
network is called terminal web. Many of the intermediate filaments of the terminal web are anchored
into the desmosomes of the lateral cell wall. In addition to the filaments, the terminal web contains the
actin-binding proteins spectrin and myosin II.

APOPTOSIS
Apoptosis is the programmed cell death. It is derived from the Greek word apo “away”+ ptosis “fall”. It
can also be called “cell suicide” because the cell’s own genes play an active role in its destruction that
distinguish it from necrosis (“cell murder”), in which healthy cells are destroyed by external processes
such as inflammation.
Apoptosis results by the activation of caspases, a group of cysteine proteases. They exist in cells as
inactive proenzymes until activated by the cellular machinery.
MORPHOLOGY OF APOPTOSIS:
Light and electron microscopy have identified the various morphological changes that occur during
apoptosis. These are as follows:
● Cell shrinkage
● Cell fragmentation.
● Collapse of cytoskeleton.
● Disassembling of Nuclear envelope.
● Release of apoptotic bodies
SIGNIFICANCE:
It is a very common process during development and in adulthood.
In the central nervous system (CNS), large numbers of neurons are produced and then die during the
remodeling that occurs during development and synapse formation.
In the immune system, apoptosis gets rid of inappropriate clones of immunocytes and is responsible for
the lytic effects of glucocorticoids on lymphocytes.
During fetal life it plays an important role in the removal of the webs between the fingers in fetal life
and regression of duct systems in the course of sexual development.
In adults, it contributes in the cyclic breakdown of the endometrium that leads to menstruation.
In epithelia, cells that lose their connections to the basal lamina and neighboring cells undergo
apoptosis that is responsible for the death of the enterocytes sloughed off the tips of intestinal villi.
Abnormal apoptosis occurs in autoimmune diseases, neurodegenerative diseases like Alzheimer
disease, and cancer. Some drugs that have been used successfully for chemotherapy appear to induce
apoptosis in cancer cells.

FUNCTIONAL SYSTEMS OF THE CELL

ENDOCYTOSIS- INGESTION BY THE CELL
Endocytosis is the reverse of exocytosis. There are various types of endocytosis like:
a. Phagocytosis (cell eating)
b. Pinocytosis (cell drinking)
c. Clathrin-mediated endocytosis
d. Caveolae-dependent uptake
e. Nonclathrin/ non caveolae endocytosis

a) PHAGOCYTOSIS:
It is the ingestion of large particles such as bacteria, whole cells or portions of degenerating tissue. Only
certain cells like tissue macrophages and some WBCs have the capacity of phagocytosis.
It is initiated when a particle such as bacterium, dead cell, or tissue debris binds with receptors on the
surface of the phagocyte. In case of the bacteria, each bacterium is usually already attached to a
specific antibody; it is the antibody that attaches to the phagocyte
receptors, dragging the bacterium along with it. This intermediation of antibodies is called opsonization
Steps:
1. Cell membrane receptors attach to the surface ligands of the particle.
2. Edges of the membrane around the points of attachment evaginate outward and
surround entire particle. Progressively more and more membrane receptors attach to
the particle ligands and form closed phagocytic vesicle.
3. Actin and other contractile fibrils in the cytoplasm surround the phagocytic vesicle and
contract around its outer edge, pushing the vesicle to the interior.
 4. Contractile proteins pinch the stem of the vesicle so completely that the vesicle
separates from the cell membrane, leaving the vesicle in the cell interior in the same
way that pinocytotic vesicles are formed.

b) PINOCYTOSIS:
It occurs continually in the cell membranes of most of cells but is especially rapid in some cells.
For example, 3% of total macrophage membrane is engulfed in the form of vesicle each minute. It is the
only means whereby large macromolecules such as proteins can enter cells.
STEPS:
1. Protein molecules attach to specialized protein receptors on the surface of the
membrane.
2. The receptors are generally concentrated in small pits called coated pits. On the inside
of the cell membrane beneath these pits is a latticework of fibrillar protein called
clathrin, as well as other proteins, perhaps including contractile filaments of actin and
myosin.
3. Once the protein molecules get attached to the receptors the pit invaginates inwards
and fibrillar proteins cause the borders to close over the attached proteins.
4. The invaginated portion of membrane breaks away from the surface of the cell.
5. Thus pinocytotic vesicle is formed.
 c) CLATHRIN-MEDIATED ENDOCYTOSIS:
It occurs at membrane indentations where the protein clathrin accumulates.
🡺 As endocytosis progresses the clathrin form a geometric array that surrounds the
endocytotic vesicle.
🡺 At the neck GTP binding protein dynamin is involved either directly or indirectly in
pinching off the vesicle.
🡺 After the vesicle is formed completely, clathrin falls of and recycles to form another
vesicle
🡺 The vesicle fuses with and dumps its contents into an early endosome.
🡺 From the early endosome new vesicle can bud off and return to the cell membrane.
🡺 Alternatively the early endosome can become a late endosome and fuse with a
lysosome in which the contents are digested by the lysosomal proteases.
❖ Clathrin-mediated endocytosis is responsible for the internalization of many
receptors and the ligands bound to them-including for example Nerve growth
factor and low density lipoproteins. It also plays a major role in synaptic function.

RAFTS AND CAVEOLAE:

Rafts are plasma membrane microdomains enriched in cholesterol and sphingolipids that are involved
in the lateral compartmentalization of molecules at the cell surface. Caveolae are caveolin-1-enriched
smooth invaginations of the plasma membrane that form a subdomain of lipid rafts.
FUNCTIONS:
They are involved in cholesterol regulation and transcytosis. cholesterol can interact directly with
caveolin, effectively limiting the protein’s ability to move around in the membrane. It is regulated by
dynamin. Caveolae are prominent in endothelial cells, where they help in the uptake of nutrients from
the blood.