cells to the basal lamina.
The best examples are found in the basal layers of
MODULE 3
Cell modification is a process that occurs after cell division where the newly
formed cells that were structurally modified so that they can perform their
function efficiently and effectively. There are three types of cell modifications;
the apical, basal and lateral.
Apical (Surface or luminal) modifications: It is specialized to carry out functions
that occur at these interfaces, including secretion, absorption, and movement
of luminal contents.
• Cilia: are membrane-covered extensions of the entire apical surface. They
beat in waves, often moving a surface coat of mucus and trapped
materials. Ciliated epithelia include ciliated pseudostratified columnar
(respiratory) epithelium and the ciliated simple columnar epithelium of the
oviducts.
• Flagella: lash-like appendage that protrudes from the cell body of certain
bacteria and eukaryotic cells termed as flagellates they are also concerned
with movement. Spermatozoa, derived from seminiferous epithelia, are
the only flagellated human cells.
• Microvilli (brush border or striated border): are plasma membrane-
covered extensions of the cell surface. Their cores are composed of parallel
actin microfilaments; these are anchored in a dense mat of filaments in the
apical cytoplasm called the terminal web. By interacting with cytoplasmic
myosin, the microfilaments can contract, shortening the microvilli.
• Pseudopods- temporary, irregular lobes formed by the amoeba and some
eukaryotic cells.
• Extra Cellular Matrix (ECM)- Compound secreted by the cell on its apical
surface. Cell wall is the extracellular structure in plant cells that
distinguishes them form animal cells. Glycoprotein the main ingredient of
ECM in animal cells.
Basal modification- The basal surface contacts the basal lamina. Because it is
the surface closest to the underlying blood supply, it often contains receptors
for blood borne factors such as hormones.
• Hemidesmosomes: are located on the inner surface of basal plasma
membranes in contact with the basal lamina. They help to attach epithelial
stratified squamous epithelium.
Lateral modification- (junctions and folding): cells attach tightly to one another
by specialized intercellular junctions.
• Tight junctions- are located near the cell apex and seal off the intercellular
space, allowing the epithelium to isolate certain body compartments (they
help keep intestinal bacteria and toxins out of the bloodstream). They act
as a barrier to regulate the movement of molecules from one cell to
another through extracellular spaces by diffusion or active transport.
• Adhering junctions consist of actin and cadherin protein filaments. Since
actin is a contractile protein, the adhering junctions are also responsible
for the change in the shape of sheets of the cells. These junctions are
meant to hold epithelial cells together.
• Gap junctions also known as communicating junctions. They allow the
cytoplasmic connection between 2 neighboring cells without the
involvement of extracellular fluid. The connexin proteins form a cylindrical
structure between the lateral surfaces of 2 adjacent epithelial cells. This
cylindrical structure with pores is called the connexon. Its main role is to
allow the free movement between the cells of ions and small molecules.
Cell cycle is the series of events that occur in a cell to prepare cell division and
to produce two new daughter cells.
Phases of cell cycle include two major activities:
1. Interphase
2. M-phase (Mitotic phase)
Interphase is the longest phase of the cell cycle process. The metabolic
activities of the cell can be observed through cell growth, production of
nutrients and enzymes and replication of DNA.
Interphase has 3 sub-stages:
1. G1 phase (Gap1 phase/Growth 1 phase)
2. S-phase (Synthesis phase)
3. G2 phase (Gap2 phase/Growth 2 phase)
G1 phase. This period will vary from different cells, the majority of cells in the
body will differentiate and implement their respective functions after the
completion of last division. The early stage of this G1 phase is being called G0
phase, and the cells began to satisfy the needs for precursor substances,
energy and enzymes of the next split synthetic DNA at the last stage of G1
phase.
S phase – The critical moment of the cell cycle. DNA doubled by replicating, at
the same time, it synthetized histones and duplicate the central particle. S
phase generally takes several hours.
G2 - is the final preparation for the division. The cell replenishes its energy
stores and synthesizes proteins necessary for chromosome manipulation.
central particles have been completed, formatting two central body and
synthesizing RNA and tubulin etc.
Cell cycle checkpoints verify whether all the cellular activities are accurately
completed at each stage of interphase.
In eukaryotic cells, there are three major checkpoints that control the cell cycle
process. They are:
1. G1 checkpoint at the G1/S transition
2. G2 checkpoint at the G2/M transition
3. Spindle checkpoint, transition from metaphase and anaphase
G1 checkpoint checks the following:
a. Cell’s size (Does the cell large increase its size or large enough for cell
division?)
b. Nutrients (Does the cell have enough reserve energy and nutrients for
cell division?)
c. DNA integrity (Is any part of the DNA damaged?)
d. Molecular signals (Does the cell receives growth factors and other
signals from neighboring cell?)
If the cell does not comply with the following factors, cell cycle will stop and
enters the G0 phase called the resting state. Some cell stays in G0 phase
permanently, while others proceed to divide if the condition of the cell
improves.
G2 checkpoint checks the following:
a. DNA integrity (Is any part of the DNA damaged?)
b. DNA replication (Is the DNA replication completed in the S phase?)
If there is an error, the cell will pause at the G2 phase and allow for some repairs.
If the damage is within the DNA, the cell cycle will be paused and let the cell
complete the DNA replication or repair it. But if the damage cell is irreparable,
the cell will undergo apoptosis or cell death. It is the self-destruction mechanism
of the cell to ensure that the damaged DNA is not passed on the daughter cells
and also important in preventing cancer. There are some cells that never or
rarely divide like matured cardiac muscle and nerve cell that permanently
retains in G0.
Metaphase checkpoint or Spindle checkpoint occurs at metaphase stage of
mitosis. It is regulated by Anaphase-promoting complex (APC). It checks whether
all chromosomes are properly attached to the spindle fibers and its alignment at
the metaphase plate. If there are mistakes, the cell delays it anaphase process.
REGULATOR MOLECULES OF THE CELL CYCLE
In addition to the internally controlled checkpoints, there are two groups of
intracellular molecules that regulate the cell cycle. These regulatory molecules
either promote progress of the cell to the next phase (positive regulation) or halt
the cycle (negative regulation).
POSITIVE REGULATION OF THE CELL CYCLE
Two groups of proteins, called cyclins and cyclin-dependent kinases (Cdks), are
responsible for the progress of the cell through the various checkpoints. The
levels of the four cyclin proteins fluctuate throughout the cell cycle in a
predictable pattern. Increases in the concentration of cyclin proteins are
triggered by both external and internal signals. After the cell moves to the next
stage of the cell cycle, the cyclins that were active in the previous stage are
degraded. Cyclins regulate the cell cycle only when they are tightly bound to
Cdks. To be fully active, the Cdk/cyclin complex must also be phosphorylated in
specific locations. Like all kinases, Cdks are enzymes (kinases) that
phosphorylate other proteins. Phosphorylation activates the protein by
changing its shape. The proteins phosphorylated by Cdks are involved in
advancing the cell to the next phase.

NEGATIVE REGULATION OF THE CELL CYCLE

The second group of cell cycle regulatory molecules are negative regulators. In
positive regulation, active molecules such as CDK/cyclin complexes cause the cell
cycle to progress. In negative regulation, active molecules halt the cell cycle. Rb,
p53, and p21 act primarily at the G1 checkpoint.

p53 is a multi-functional protein that has a major impact on the commitment of

a cell to division because it acts when there is damaged DNA in cells that are
undergoing the preparatory processes during G1. If damaged DNA is detected,
p53 halts the cell cycle and recruits enzymes to repair the DNA. If the DNA
cannot be repaired, p53 can trigger apoptosis, or cell suicide, to prevent the
duplication of damaged chromosomes. As p53 levels rise, the production of p21
is triggered. p21 enforces the halt in the cycle dictated by p53 by binding to and
inhibiting the activity of the Cdk/cyclin complexes. As a cell is exposed to more
stress, higher levels of p53 and p21 accumulate, making it less likely that the cell
will move into the S phase.

When Rb is bound to transcription factors, production of proteins necessary for

the G1/S transition is blocked. As the cell increases in size, Rb is slowly
phosphorylated until it becomes inactivated. Rb releases the transcription
factors, which can now turn on the gene that produces the transition protein,
and this particular block is removed. For the cell to move past each of the
checkpoints, all positive regulators must be “turned on, and all negative
regulators must be “turned off.”