Cell Communication and Cell Cycle

AP Biology
Feedback Loops
H omeostasis
● Steady state or internal balance
● Cells maintain a relatively constant internal
environment even when the external environment
changes significantly
○ Typical internal condition is the set point
○ Fluctuations in that condition above or below
the set point serve as the stimulus
○ A receptor or sensor detects the stimulus and
triggers a response, an activity that returns
the condition to the set point
Negative Feedback
● The response reduces the
stimulus
● Ex. When you exercise, you
produce heat, which increases
your body temperature. Your
nervous system detects this
increases and triggers sweating.
As your sweat evaporates, your
skin cools, returning your body
to its set point.
Positive Feedback
● The stimulus is amplified in order to
complete a process; then the condition
returns to the set point
● Ex. During childbirth, the pressure of
the baby’s head against the uterus
stimulates contractions. The
contractions result in greater pressure,
thereby stimulating more contractions
and then more pressure. This
continues until the baby is born.
Positive Feedback
● Fruit Ripening
Signal Transduction Pathways
 Methods Used by Cells to Communicate
● Autocrine signaling - a cell sends a signal to itself
● Juxtacrine signaling - cells communicate with
adjacent cells through direct contact
○ Ex. plasmodesmata connect plant cells and
gap junctions connect animal cells Autocrine Juxtacrine
○ Ex. glycoproteins on one cell interact with
glycoproteins on another cell
● Paracrine signaling - cells communicate to nearby
cells by releasing chemical messengers
○ Ex. neurotransmitters released into a synapse
● Endocrine signaling - cells communicate to cells far
away by releasing chemical messengers that are Paracrine Endocrine
carried to the target cell
○ Ex. adrenaline is produced by adrenal glands,
released into the bloodstream, and carried to
the heart and other muscles
Methods Used by Cells to Communicate (Autocrine)
Methods Used by Cells to Communicate (Juxtacrine)
Methods Used by Cells to Communicate (Paracrine)

Synapse

Plant defenses

How bacteria Video: quorum

“talk” sensing

Morphogens
Methods Used by Cells to Communicate (Endocrine)
 Cell Junctions
● Proteins also connect cells
through intercellular junctions,
sometimes creating open
channels.
● Gap junctions and plasmodesmata
can be used for cell
communication
Signal Transduction Pathways
In all forms of cell signaling, a signal is converted to a cellular response in three
steps -

1. Reception - signaling molecule binds

to the receptor protein
2. Transduction - the signal is converted
into a form that can produce a cellular
response
3. Response - the transduced signal
triggers a cellular response
Step 1 - Reception
● A signal molecule, a ligand, binds to a receptor protein in a lock and key
fashion, causing the receptor to change shape.
● Most receptor proteins are in the cell membrane but some are inside the cell.
○ Hydrophilic ligands bind to plasma membrane receptors
○ Small or hydrophobic ligands can pass through the membrane and attach
to intracellular receptors (ex. steroid hormones like testosterone)
● The three most common types of membrane receptor proteins - This binding
● G-protein coupled receptors is highly
● Receptor tyrosine kinases specific
(must be the
● Ion channel receptors right shape).
G-Protein Coupled Receptors
● G proteins bind the energy-rich GTP (very
similar to ATP- source of energy)
● G proteins are all very similar in structure
● GPCR systems are extremely widespread
and diverse in their functions
G protein-coupled Plasma Inactive
receptor Activated
membrane enzyme
receptor Signaling
molecule
1 Enzyme
GDP
2 GDP
CYTOPLASM G protein GTP
(inactive)
Activated
enzyme

Ex. Epinephrine (ligand) attaches to a i

beta-adrenergic receptor (a type of 3 GTP GDP
G-protein coupled receptor) in the P
Cellular 4
heart to increase contractions response
G-Protein Coupled Receptors (GCPR )
1. A ligand binds to the receptor on
the outside of the membrane

2. The receptor changes shape and

activates a G protein on the inside
G protein-coupled Plasma Inactive
3. The G proteins exchanges GDP receptor membrane
Activated
enzyme
receptor Signaling
for GTP and then activates other molecule
Enzyme
enzymes or ion channels 1
GDP
2 GDP
CYTOPLASM G protein GTP
(inactive)
4. These enzymes produce Activated
enzyme
second messengers like cAMP,
IP3 or DAG i

3 GTP GDP
Ex. Epinephrine (ligand) attaches to a P
beta-adrenergic receptor (GPCR) → activates Cellular 4
adenylyl cyclase → increases cAMP → the heart response
increases contractions
 Receptor Tyrosine Kinases (RTK )
● Receptor tyrosine
kinases (RTKs) are
membrane receptors
that transfer phosphate
groups from ATP to the
tyrosine amino acid on a
protein
● The phosphorylation by
RTK acts as an “on”
switch triggering a
cascade of cell events

Ex. Insulin (ligand) attaches to an Insulin Receptor (a type of

receptor tyrosine kinase) to initiate the transport of GLUT4
Transporters into the cell membrane so glucose can enter the cell
 Receptor Tyrosine Kinases (RTK )
● A ligand binds to the
extracellular domain of
RTK
● 2 receptor molecules
come together to form a
dimer
● Each receptor
phosphorylates its
partner
● The phosphorylated
tyrosines act as docking
sites for relay proteins
● Relay proteins activate a
pathway such as cell
division, growth, or Ex. Insulin (ligand) attaches to an Insulin Receptor (a type of
receptor tyrosine kinase) to initiate the transport of GLUT4
differentiation Transporters into the cell membrane so glucose can enter the cell
 Signaling
molecule

Ion Channel Receptors (ligand)

● An ion channel receptor acts as a

gate that opens and closes when Ligand-gated Plasma
ion channel receptor
the receptor changes shape membrane
● When a signal molecule binds as 2
Gate open
a ligand to the receptor, the gate
allows specific ions, such as Na+
or Ca2+, through a channel in the
receptor Cellular
response
Ex. Acetylcholine (ligand) attaches to
an ACh Receptor (a type of ion 3 Gate closed
channel receptor), which causes the
channel to open and allows sodium to
enter the cell, leading to muscle
contraction
Step 2 - Transduction
● Molecular interactions relay signals from receptors to target molecules in
the cell

● Multistep pathways

○ Can amplify a signal (by activating multiple copies of the next component
in the pathway)

○ Provide more opportunities for coordination and regulation

● At each step in a pathway, the signal is transduced into a different form,

commonly a conformational (shape) change in a protein.
Transduction - Phosphorylation
Like “hot potato” with phosphates

● In this process, a series of protein

kinases (signal transmitters) add a
phosphate to the next one in line,
activating it
● Phosphatase enzymes then remove
the phosphates

inactive active
 Transduction - Secondary Messengers
Secondary messengers are small molecules/ions that
relay signals received by receptors to proteins that will
lead to a cellular response
Common secondary messengers -
● cAMP (cyclic AMP)
● IP3
● DAG
● Calcium
○ Ca2+ can function as a second messenger
because its concentration in the cytosol is
normally much lower than the concentration
outside the cell; thus a small change in the
number of calcium ions represents a relatively
large percentage change in calcium
concentration
Transduction - Scaffolding Proteins
Scaffolding proteins can
increase the signal transduction
efficiency.
Is a large molecule that bind to a
receptor or relay protein
“Organizer” of a signaling
pathway
Hold multiple signaling Each is activated
All three activated at
molecules together in one place the same time - speeds separately = inefficient
so that signals are transferred up the signal because
molecules do not have
quickly
to diffuse through the
cytoplasm
Step 3 - Response
There can be many possible responses to a
cell signal -
● The same signal molecule can lead to
different responses
● The signal can also stimulate an
activator or inhibitor molecule
● The signal can also activate multiple
receptors and different responses
● Example of responses - turn
transcription on/off or regulate
activity of proteins in cytoplasm
Types of Responses
Signaling
molecule

Receptor

Relay
molecules Activation
or inhibition

Response 4 Response 5
Response 1 Response 2 Response 3

Cell A. Pathway leads Cell B. Pathway branches, Cell C. Cross-talk occurs Cell D. Different receptor
to a single response. leading to two responses. between two pathways. leads to a different response.
Stopping the Response
The signal response is terminated
quickly when the ligand detaches from
the receptor
Pathway Diagram Analysis
Pathway diagrams illustrate chemical or signaling pathways and can provide important information such as:
● What proteins/enzymes/molecules are activators in the pathway
● What proteins/enzymes molecules are inhibitors in the pathway
● Whether or not transcription for a gene is induced or repressed.
● What molecules are acting as second messengers (for cell signaling pathways)
Signaling Pathway Symbols
Activation of a molecule Inhibition of a molecule
or cellular process or cellular process

Practice:
What is p53’s function in the pathway?
a. p53 leads to the inhibition of the cell cycle
What is MDM2’s function in the pathway?
b. MDM2 inhibits p53, which would allow for initiation of the cell cycle.
How does DNA damage affect the outcome of the pathway?
c. DNA damage inhibits MDM2, which would allow p53 to be active, thus inhibiting the cell cycle.
Understanding Diagram Symbols
→ (arrow) Activation / Stimulation

⊣ (flat or blunt end) Inhibition / Suppression

— (plain line) Binding / Association

↔ (double arrow) Indirect Activation / Multi-step Effect

⇢ (dashed arrow) Indirect Activation / Multi-step Effect

⚫ or rounded or block-like shape Molecule / Protein

⚪ (ligand symbol) Signaling Molecule

+ (plus sign) increases or enhances the activity of another process or

molecule

– (minus sign) decreases or represses the activity of another process or

molecule
Sweet Receptor Pathway Example

Transduction of Sweet Taste

● Binding of a sugar molecule to a receptor cell

initiates a signal transduction pathway involving
cyclic AMP and protein kinase A.
● K+ channels in the membrane close, and the
membrane depolarizes
● Voltage-gated calcium Ca2+ channels open, and
Ca2+ diffuses into the receptor cell.
● Synaptic vesicles release neurotransmitters,
sending signals to the sensory neuron.
The Cell Cycle
Functions of the Cell Cycle
The Cell Cycle
● One cell divides, forming two identical cells
○ Genetics material is divided during mitosis
○ Organelles and cytoplasm are divided
during cytokinesis
● Unicellular organisms - used for reproduction
○ Called binary fission
● Multicellular organisms - used for growth and
repair
The Cell Cycle
● All the DNA in a cell constitutes the cell’s
genome

● A genome can consist of a single DNA molecule

(common in prokaryotic cells) or a number of
DNA molecules (common in eukaryotic cells)

● DNA molecules in a cell are packaged into

chromosomes

● The DNA molecule of a chromosome carries

several hundred to a few thousand genes
The Cell Cycle
● Eukaryotic chromosomes consist of chromatin, a
complex of DNA and protein that condenses
during cell division

● Every eukaryotic species has a characteristic

number of chromosomes in each cell nucleus

● Somatic cells (non reproductive cells) have two

sets of chromosomes

● Gametes (reproductive cells: sperm and eggs)

have half as many chromosomes as somatic cells
Replicated Chromosome

● Before cell division, DNA is replicated and the chromosomes condense

● Each duplicated chromosome has two sister chromatids ( joined copies of the
original chromosome), attached along their lengths by cohesins
● The centromere is where the two chromatids are most closely attached by a
protein called cohesin
● The centromere consists of repetitive DNA sequences that are unique to the
centromere region and serves as a structural foundation for the kinetochore
complex
Organelles Involved in the Cell Cycle
Nucleus
● Protects the DNA
Centrosome
● microtubule organizing center (MTOC); the
microtubules become spindle fibers; the anchoring
point for microtubules
Cytoskeleton
● Includes the centrioles, which are responsible for
the spindle fibers that attach to the kinetochore
and guide the chromosomes during mitosis; the
spindle fibers shorten during anaphase, pulling the
sister chromatids apart
Overview of the Cell Cycle
Interphase
Cells spend 90% of their time in interphase
● G1 = 1st Gap G0; cell continues doing its job
○ Everyday tasks such as making proteins until it receives a signal to
○ Cell grows reenter G1 to get ready to divide
If the cell receives a signal to divide, it moves on to the next phases:
DN
● S = DNA Synthesis A
chr in the
om
○ Copies genetics material (so each cell gets a copy) atin form
(stri of
● G2 = 2nd Gap ngy
)
○ Prepares for division
○ Cell grows more
○ Produces proteins, organelles, and membranes
Mitosis
The DNA is divided between two daughter nuclei in four phases -

1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
Prophase
● Chromatin condenses into chromosomes
● Centrioles organize the mitotic spindle (in
animal cells) and move to opposite ends of
DNA was in
the cell this form in
● Protein fibers, such as microtubules and interphase.
microfilaments form from the centrosomes
● The nucleolus disappears
● The nuclear membrane breaks down

Now it is in this
form.
Metaphase

● Spindle fibers (attached to kinetochores)

coordinate movement
● Chromosomes line up in the middle of the
cell
● The kinetochore built on the centromere is
crucial for attaching to spindle microtubules,
which pull sister chromatids apart and ensure
that each new cell receives a complete set of
chromosomes
Anaphase
● Sister chromatids separate at kinetochores
○ Proteins holding the sister chromatids
together are inactivated
○ Pulled by motor proteins “walking” along
microtubules
● Poles move farther apart
Telophase
● Chromosomes arrive at opposite poles
● Daughter nuclei form
● Chromosomes disperse
● Spindle fibers disperse
● Cytokinesis begins
Cytokinesis
Animal Cells Plant Cells

● Microfilaments contract, forming ● Cell plate forms

a cleavage furrow ● Vesicles from the Golgi fuse to
form two cell membranes
● New cell wall laid down between
the cell membranes
Chromosome Duplication and Distribution in the Cell Cycle
The Cell Cycle
Mitosis in an Animal Cell
Mitosis in an Animal Cell
Mitosis in a Plant Cell
Summary of Mitosis
Binary Fission in Bacteria
•Prokaryotes (bacteria and Because prokaryotes evolved before
archaea) reproduce by a type of eukaryotes, mitosis probably evolved
cell division called binary fission from binary fission

•In binary fission, the chromosome

replicates, and the two daughter
chromosomes actively move apart
•The plasma membrane pinches
inward, dividing the cell into two
Bacterial Cell Division by Binary Fission
Cell Cycle Regulation
Analogy for the Cell Cycle Control System
Cell Cycle Checkpoints
Checkpoints serve as control points where stop and go-ahead signals can regulate
the cell cycle (controlled by signals inside and outside the cell).
M Checkpoint-
G2 Checkpoint- -When the DNA lines up in the middle
Did the DNA copy correctly in the S (metaphase), will each cell get the
phase? same amount of DNA?
Pass- Cell goes to mitosis Pass- cell divides
Fail - apoptosis Fail - Apoptosis

G1 checkpoint-
-Do I need a new cell?
-Is this cell healthy?
-Are there enough nutrients
to divide?
Pass - Cell enters S phase
Fail - Goes to G0
Internal Signals - Cyclins and Cyclin-Dependent Kinases
● “Go” signals at checkpoints results in changes in molecular signals in the
cytoplasm
● Kinases - proteins that activate or inactivate other proteins by phosphorylating
them
○ cyclin-dependent kinases (Cdks) - kinases that are only active when attached
to a cyclin
● Cyclin - a protein that fluctuates in concentration in the cell
Internal Signals - Cyclins and Cyclin-Dependent Kinases
● The concentration on Cdks does
not fluctuate.
● The concentration of cyclins
does. Certain cyclins are made at
certain times during the cell
cycle, and their concentration
will rise and fall. Cyclins are also
destroyed after they are no
longer needed by the cell.
● Cdks are only active (initiate the
next step of the cell cycle) when
attached to a cyclin.
MPF (maturation-promoting factor)
MPF is a cyclin-Cdk complex that triggers a cell’s passage past the G2
checkpoint into the M phase

Peaks of MPF activity correspond to the peaks of cyclin concentration

MPF acts both as a kinase and indirectly through activating other kinases
Rise and Fall of Cyclin Concentration During Cell Cycle
Molecular Control of the Cell Cycle at the G2 Checkpoint
External Signals -
● Growth factors are released by some cells and
stimulate surrounding cells to divide
○ Ex. Platelets release platelet-derived growth
factor (PDGF). Fibroblasts (connective tissue)
have receptors for PDGF. When PDGF binds
to the receptors, a signal transduction
pathway stimulates fibroblast division.
● Density-dependent inhibition - crowded cells
stop dividing
● Anchorage dependence - to divide, cell must be
attached to something
Density dependent inhibition and anchorage dependence of cell
division
Cancer

Cancer cells bypass cell cycle controls -

● Cancer cells do not respond to normal sigals that regulate the cell cycle
● They do not stop dividing when growth factors are depleted
○ They may make their own growth factor
○ May have an abnormal cell cycle control system
○ May convey a growth factor’s signal without the presence of the growth
factor
● Cells that acquire the ability to divide indefinitely have undergone
transformation
Cancer- Malignant

normal cell cancer cell

bloodstream
Cancer
The immune system normally recognizes a cells conversion from a normal cell to a
cancer cell and destroys it. If it is not destroyed, a tumor can form.

○ Benign - tumor stays in the same place; most benign tumors do not cause
serious problems depending on their location
○ Malignant - invade surrounding tissues and undergo metastasis - the
spread of cancer cells to other parts of the body, where they may form
additional tumors
○ The majority of cancer cells have lost the ability to repair DNA damage
What causes cancer
● Defects and disruptions in genes that regulate cell growth and division
○ An oncogene is a mutated gene that has the potential to cause
cancer
● Carcinogens- things that cause cancer like smoking, chewing tobacco,
radiation exposure, some viral infections.
● Cells fail to respond to external growth regulators and/or internal
regulators
● Many cancer cells have a defect in the p53 gene which normally halts
the cell cycle until all chromosomes have been replicated
Proto-Oncogenes
● Normal function - when activated,
they signal for cell division to start
(G1 checkpoint)
● Mutation function - the gene is
always activated, so it continues to
divide (ignores the G1 checkpoint)
● Once mutated, a proto-oncogene is
called an oncogene.
● Dominant - only one copy of the
defective gene is needed to impact
the cell
Tumor Suppressor Genes
● Normal function - slow cell division,
repair mistakes, or apoptosis
● Mutated function - cell does not
stop division if mistakes are found
● Recessive - both copies of the gene
must be mutated to impact the cell
 Tumor Suppressor Gene - p53

● Function: the p53 protein, helps regulate the

cell cycle, repair damaged DNA, and trigger
apoptosis if damage cannot be repaired
● Role in checkpoints: It’s especially active at the
G₁/S checkpoint, preventing cells with damaged
DNA from entering S phase
● Tumor suppression: it halts the division of
potentially cancerous cells, p53 acts as a
guardian of the genome.
● Mutation effect: When p53 is mutated or
inactivated, cells can divide
uncontrollably—leading to tumor formation
Skin Cancer is the Most Common form of Cancer - Watch
your moles!
 I will not ask you about the details of these
treatments. This is just FYI. You can learn more by
Cancer Treatments clicking on the blue links.

● Chemotherapy- drugs disrupt any cells going through mitosis; used in wide
spread cancers
● Radiation- high energy beams (mostly X rays) are emitted onto a cancerous
body part, causing mutations in the DNA to the point where the cell cannot
divide
● Immunotherapy- trains the immune system to recognize cancerous cells and
kill them off
● Precision Medicine - aka targeted therapy; uses specific medicines that can
interfere with proteins that help cancerous cells proliferate
● Hormone Therapy- slows down the growth of cancer by either stopping the
patient from producing hormones or interfering with hormone behavior (as in
prostate and breast cancers)
● Gene Therapy- uses CRISPR to fix mutations on genes that are causing cells to
be cancerous