BIOLOGY FOR AP® COURSES

Chapter 9 CELL COMMUNICATION

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Cell is an independent functional unit - like a country
Cell is an independent functional unit - like a country

No free access is possible generally (with exceptions)

Cell has receptors and channels for
selective transport

Receptor tyrosine kinases

Channels

GPC Receptors
α
GTP

γ β
Nuclear/cytoplasmic
receptors
Effector
Notch type receptors
How do cells communicate in the neighborhood
and long distance?

Or Do they at all?
Yes, they do through a process called signaling
Four categories of signaling
4 signaling categories
1. Autocrine signaling: signaling cells that produce
ligands also bind to the ligand - signal and target cell
can be the same (cell death signaling)
2. Direct signaling across gap junctions:
intracellular mediators that allow small signaling
molecules to move between cells
3. Paracrine signaling: one cell releases ligand
another cell takes it - move by diffusion through
extracellular matrix, examples include synaptic signals and
neurotransmitters

4. Endocrine signaling: ligand poured into blood and

transported to distant parts in the body - typically
produce a slower response with a long-lasting effect
(e.g., hormones)
Another category is juxtracrine secretion
 Two important requirements for signaling
1. Signal
2. Receptor

Chemical molecule as signal

Called ligand or agonist

Receptor on the cell

surface recognizes
specific ligand

On this basis there are different signaling categories

For Autocrine signaling the ligand is
secreted and used by same cell

Some cancer cells

use it for making a
tumor
Paracrine Signaling Example

Some chemicals
(neurotransmitter) travel
the synaptic gap and
activate neighboring
neuron.

Enzymes can degrade

neurotransmitters -
terminate the signal.
Endocrine

Secreted by one organ (thyroid or Pancreas)

Move in blood
Reach a target cell at different location in the body

Insulin is a hormone
 pecial ligands
Hydrophobic ligand can pass cell membrane easily
ut still need receptors inside the cell
example:
Estrogen (E, red circle) passes
cell membrane attaches
to
Estrogen receptor (ER, blue
triangle).

E-ER Complex moves to

nucleus activates
mitogenic factors – can
cause breast cancer.

Estrogen mimics can

prevent this cancer
More Small hydrophobic ligands

Steroid hormones have similar chemical

structures to their precursor,
cholesterol.
Different Cell-Surface Receptors

• Ion channel-linked receptors

• G-protein-linked receptors
• Enzyme-linked receptors
Ion channels
Example: Ion Channel-Linked Receptor

Ligand Gated ion channels - pore through the

plasma membrane - opens when the signaling molecule
binds - allows ions to flow into or out of the cell.
Voltage Gated ion channels: same function but
controlled by voltage changes across the membrane
G-protein Coupled/linked
G-Protein-linked Receptor

Example
Parathyroid hormone
receptor – opens Ca2+
channels

Rhodopsin
– helps in vision
Enzyme activating receptors
 Enzyme-linked Receptor Example

Receptor tyrosine kinase

Ligand binds in extracellular domain
causing dimerization of receptor.

This causes
transphosphorylation of
tyrosine residues in the
intracellular domains of the
receptor molecules

This then triggers a

A B downstream cellular response
thatAends on DNA in nucleus
phosphorylates B& B
phosphorylates A – called
transphosphorylation
 Propagation of the Signal - 1
• Signal transduction: when a ligand binds to a
receptor and the signal is transmitted through the
cell membrane and into the cytoplasm continuing
the signal
• Dimerization: two receptors bind to each
other to form a stable complex
• Propagation: chain of events
• phosphorylation or
• second messengers,
• Activated proteins thus follow ligand
binding to a receptor
• Signal integration: signals from two or more
different cell-surface receptors can merge to
activate the same response in the cell
 Example of EGF/EGFR
(Phosphorylation)

The epidermal growth factor

(EGF) receptor (EGFR) is a
receptor tyrosine kinase involved
in the regulation of cell growth,
wound healing, and tissue repair.

When EGF binds to the EGFR, a

cascade of downstream events
causes the cell to grow and
divide.

Follow the arrows till the signal

reaches nucleus.

If EGFR is activated at
inappropriate times, uncontrolled
cell growth (cancer) may occur.
 Specifics of phosphorylation in Intracellular Signaling

HO HO CH3

R
Phosphorylation R
A phosphate group (PO4-3 ) is
added to the amino acids serine,
threonine, or tyrosine.

Kinase: the enzyme that HO

catalyzes the transfer of a
phosphate group
R
Phosphatase: the enzyme
that removes phosphate group
Cell signaling general

https://www.youtube.com/watch?v=-dbRterutHY
Cell Signaling

https://www.dnalc.org/resources/3d/cellsignals.html
 Propagation of the Signal - 2
Through Secondary messengers: After the ligand
binds a receptor a new new molecule is activated and
propagates the signal.

• Example of a second messenger: This diagram shows the mechanism for the
formation of cyclic AMP (cAMP). cAMP serves as a second messenger to activate
or inactivate proteins within the cell. Termination of the signal occurs when an
enzyme called phosphodiesterase converts cAMP into AMP.
Secondary messengers – another example

The enzyme
phospholipase C is
activated by receptor
tyrosine kinase

Phospholipase C breaks
down PIP2 into IP3 and
DAG, both of which
serve as second
messengers.
Actual signal transduction is complex cross-reacting network

By cybertory - This file was derived from: Signal transduction v1.png, CC BY-SA 3.0,
https://commons.wikimedia.org/w/index.php?curid=12081090
 Responses to cell signaling
• Increase in cellular metabolism
• Adrenaline activates β-adrenergic receptors
• These increase cyclic AMP (cAMP), which
activates PKA.
• PKA phosphorylates two enzymes, which
lead to a ready supply of glucose and an
increase in metabolism
• Cell growth
• Growth factors bind to tyrosine kinases
• These initiate a pathway (including a G-
protein called RAS) which activates MAP
kinase pathway
• MAP Kinase stimulates protein expression
that eventually leads to cell division
Response to the signal: Gene Expression
ERK is a MAP kinase that activates
translation when it is phosphorylated.

ERK phosphorylates MNK1, which in turn

phosphorylates eIF-4E.

When eIF-4E becomes phosphorylated,

the mRNA unfolds, allowing protein
synthesis in the nucleus to begin.
Cell Death: Apoptosis

Death ligands can activate signaling cascade

Which activate caspases (enzymes that digest cellular organelles)

 Signaling in single-celled organisms: Yeast
• Yeast cells can communicate by
releasing a signaling molecule
called mating factor.

• Mating factor binds to cell-surface

receptors in nearby yeast cells.

• They stop their normal growth

cycles and initiate a cell signaling
cascade that includes protein
kinases and GTP-binding proteins
that are similar to G-proteins.

• Finally the two haploid cells fuse

to from a diploid cell
 Signaling in
single-celled
organisms:
• Bacteria
In bacteria,
population density is
often the key factor
for signaling.

• Bacterial signaling is
thus call quorum
sensing.

• It utilizes molecules
called autoinducers.
Cell signaling in bacteria and new idea of antibiotics

https://www.ted.com/talks/bonnie_bassler_how_bacteria_talk
What did you learn today

Key terms
… kinase – phosphorylation
…. Apoptosis
…. Quorum formation
… types of signaling
… endocrine
…. Exocrine …… find it yourself…..?