Cells –HL C 2.

1 Chemical Signaling

Guiding Questions

“How do cells distinguish between the many signals that they receive?”

“What interactions occur inside animal cells in response to chemical signals?”

Syllabus Objectives

Receptors as proteins with

C2.1.1 binding sites for specific Students should use the term “ligand” for the signalling chemical.
signalling chemicals
Cell signalling by bacteria in Include the example of bioluminescence in the marine bacterium Vibrio
C2.1.2
quorum sensing fischeri.
Hormones, neurotransmitters,
cytokines and calcium ions as
C2.1.3 examples of functional Students should appreciate the differences between these categories.
categories of signalling
chemicals in animals
Consider reasons for a wide range of chemical substances being used as
Chemical diversity of
signalling chemicals. Include amines, proteins and steroids as chemical groups
C2.1.4 hormones and
of hormones. A range of substances can serve as neurotransmitters including
neurotransmitters
amino acids, peptides, amines and nitrous oxide.
Localized and distant effects of Contrasts can be drawn between hormones transported by the blood system
C2.1.5
signalling molecules and neurotransmitters that diffuse across a synaptic gap.
Differences between
transmembrane receptors in a
Include distribution of hydrophilic or hydrophobic amino acids in the receptor
C2.1.6 plasma membrane and
and whether the signalling chemical penetrates the cell or remains outside.
intracellular receptors in the
cytoplasm or nucleus
Initiation of signal
Students should understand that the binding of a signalling chemical to a
C2.1.7 transduction pathways by
receptor sets off a sequence of responses within the cell.
receptors
Transmembrane receptors for Use the acetylcholine receptor as an example. Binding to a receptor causes the
neurotransmitters and opening of an ion channel in the receptor that allows positively charged ions to
C2.1.8
changes to membrane diffuse into the cell. This changes the voltage across the plasma membrane,
potential which may cause other changes.
Students should understand how G protein-coupled receptors convey a signal
Transmembrane receptors
C2.1.9 into cells. They should appreciate that there are many such receptors in
that activate G proteins
humans.
Mechanism of action of Include the roles of a G protein and cyclic AMP (cAMP) as the second
C2.1.10 epinephrine (adrenaline) messenger.
receptors
Use the protein hormone insulin as an example. Limit this to binding of insulin
Transmembrane receptors to a receptor in the plasma membrane, causing phosphorylation of tyrosine
C2.1.11
with tyrosine kinase activity inside a cell. This leads to a sequence of reactions ending with movement of
vesicles containing glucose transporters to the plasma membrane.
Use the steroid hormones oestradiol, progesterone and testosterone as
Intracellular receptors that examples. Students should understand that the signalling chemical binds to a
C2.1.12
affect gene expression site on a receptor, activating it. The activated receptor binds to specific DNA
sequences to promote gene transcription.
Effects of the hormones
For oestradiol, limit to cells in the hypothalamus that secrete gonadotropin-
C2.1.13 oestradiol and progesterone
releasing hormone. For progesterone, limit to cells in the endometrium.
on target cells
Regulation of cell signalling
Limit to an understanding of the difference between these two forms of
C2.1.14 pathways by positive and
regulation and a brief outline of one example of each.
negative feedback

1|Page
Receptors as proteins with binding sites for specific signalling chemicals:

Cells communicate with each

other by sending and receiving
chemical signalling molecules
called ligands. Typically, one cell
produces chemical substances as
messengers, and another one
(often called the target cell)
receives them using a receptor.

Annotate the diagram below to describe the function of the ligand and the receptor:

Receptors are similar to enzymes, yet there are multiple differences. Compare and contrast the two:
Enzymes Receptors

2|Page
Cell signalling by bacteria in quorum sensing:

In legal terms “A quorum is the minimum number of members of a group

necessary to constitute the group at a meeting. In a deliberative assembly
(a body that uses parliamentary procedure, such as a legislature), a
quorum is necessary to conduct the business of that group”.

Bacteria have also been found to have a quorum before an action (e.g. bioluminiscence, pathogenicity,…) can
take place. This feature is called quorum sensing.

Quorum sensing is a form of cell signaling in bacteria based

on the number of cells, which allows communication and a
common decision on a specific action.

This quorum is perceived with the help of signalling

molecules (autoinducers), which at a low rate (due to the low
number of cells) will only result in individual behaviour to
that chemical signal. In high concentrations the molecules
diffuse between the cells and bind to receptors, resulting in a
switch in activity based on sensing a “quorum”.

With an increase of population density all cells

receive more signals from other molecules,
resulting in an a group behaviour which is much
more powerful than an individual action.

An example of quorum sensing with a distinct

biological purpose is found in the Hawaiian
bobtail squid, where the bacterium vibrio fischeri
displays an act of quorum sensing. Watch the
video clip and answer the questions:
https://1drv.ms/v/s!Au8ZKE_EDcrQhLRxypqqdqxVteuW3Q?e=CgH0u1

What is vibrium fisheri?

What special property does vibrium fisheri have?

Under which conditions does the bacterium glow (bioluminiscence)? Explain how this works:

3|Page
Where does vibrium fisheri live and how does this represent a form of interspecific relationship?

Now use this video https://1drv.ms/v/s!Au8ZKE_EDcrQhLRwfSAXXgxc6pTd2A?e=fyoxxi and answer the

questions below:

What is the name of the system of genes which activates the bioluminscence?

What function do the autoinducers, synthesized by the lux I gene from this system, have on Lux R?

4|Page
Hormones, neurotransmitters, cytokines and calcium ions as examples of functional categories of signalling
chemicals in animals:

Hormones
Hormones are chemical signalling molecules
produced by endocrine glands in the body. They
are transported in the bloodstream. Hormones
regulate activities of the target cells by promoting
or inhibiting specific processes. They can persist in
the body for hours after being screted.

Examples of hormones are TSH and T4, which are

released by the thyroid gland, or progesterone and
estrogen released by the ovaries.

Neurotransmitter
Neurotransmitters are chemicals that transmit
signals across a 20-40nm wide synapse between
two neurons in the nervous system. The
neurotransmitter is released from the presynaptic
neuron and binds to receptors in the plasma
membrane of the postsynaptic neuron. This is
where a nerve impulse is initiated.

Examples of neurotransmitters are acetylcholine,

serotonine, dopamine or adrenaline.

Cytokines
Cytokines are small proteins which act as signalling
chemicals secreted by many different types of cells
– often by cells of the immune system. Cytokines
bind to recepetors embedded in the plasma
membrane of nearby cells. Often, cytokines have
signalling roles in inflammation and other defense
responses. They also have roles in the cell
proliferation and development of embryos.

Examples of cytokines are interleukins, interferons

or chemoleukins, which are produced by different
classes of white blood cels.

5|Page
 Calcium ions
Calcium ions are used for cell signalling in both
muscle fibres and neurons. The release of calcium
ions in muscles from a specialized endoplasmic
reticulum (sarcoplasmic reticulum) causes proteins
(troponin) on muscle fibres to change position.

Troponin normally block binding sites on muscle

fibers preventing muscle contraction. With
proteins having moved out of the way, a successful
muscle contraction can take place and the muscle
shortens.

Read through the information in the table above and compare the different types of signaling chemicals:
Types of messengers
Hormones Neurotransmitters Cytokines Calcium ions
Released
from…

Target cell

Response

Examples

6|Page
Chemical diversity of hormones and neurotransmitters

Hormones:
These kind of messengers can be grouped into three different chemical categories:

Hormones can be small, non-polar, hydrophobic molecules that diffuse through the cell membrane to reach
receptors in the nucleus or cytoplasm, such as testosterone or progesterone. Hormones can also be water-
soluble molecules that bind to receptors in the plasma membrane, such as insulin or glucagon, or epinephrine
(adrenaline).

Neurotransmitters:

Neurotransmitters are chemically diverse and include amines, amino acids or polypeptides and even gases such
as nitric oxide – which acts on receptors in the brain and other parts of the central nervous system.

7|Page
 Localized and distant effects of signalling molecules:

Signalling molecules can work on target cells nearby or far away after having been transported in the blood
stream. Compare the two types of effects:
Localized effects Distant effects
Differences
Similarities
Examples

8|Page
Differences between transmembrane receptors in a plasma membrane and intracellular receptors in the
cytoplasm or nucleus:

Depending on whether signalling molecules can enter the target cell or not, they can bind either to receptors
which are embedded within the plasma membrane (transmembrane receptors) or receptors which are found
inside the cytoplasm or nucleus (intracellular receptors).

Transmembrane receptors:

In many cases ligands (e.g. peptide hormones such as insulin) bind to a receptor in the membrane. This causes a
change in chape of the receptor that results in a signal to be relayed across the membrane to the cytoplasm.
The ligand binding site of the integral membrane protein is hydrophilic, while the parts that traverse the
membrane are hydrophobic so that the molecules can be anchored. The areas near the phosphate heads of the
protein are hydrophilic again.

Intracellular receptors:

Intracellular receptors such as steroid receptors are present as soluble proteins in the cytoplasm. Steroid
hormones are lipid soluble, so they diffuse from the blood stream across the plasma membrane and then bind
to the receptor molecule. Intracellular receptors have hydrophilic amino acids so they remain dissolved in the
aquaeous fluids of the cytpoplasm or nucleus.
9|Page
Initiation of signal transduction pathways by receptors:

When a signalling chemical binds to a receptor, a

sequence of interactions in the cell is triggered.
This is called a signal transduction pathway.

Types of responses:

• Regulation of protein activity (e.g. by

opening or closing an ion channel)
• Regulation of protein synthesis through
gene expression
• Regulation of enzyme activity
• Rearrangement of the cytoskeleton of the
cell
• Death of the cell (apoptosis)

Transmembrane receptors for neurotransmitters and changes to membrane potential:

Some transmembrane receptors

in the neurons of the nervous
system are ligand gated. Upon
binding of a neurotransmitter
(e.g. Acetylcholine) the channel
undergoes a change in
conformation (change) and
opens, allowing sodium ions to
flow across the membrane down
their concentration gradient. This
depolarizes the membrane and
changes the membrane
potential.

Explain in your own words: What is a ligand-gated receptor?

What effect does the binding of a ligand to a ligand-gated receptor have?

What is the consequence of a change in membrane potential of a neuron?

10 | P a g e
Transmembrane receptors that activate G proteins:

G proteins are membrane bound protein

receptors which bind to GTP, usually
activated by the binding of a hormone or
other ligand. GTP is an energy-rich nucleotide
similar to ATP. After activation of the G
protein a number of signals can be
transmitted.

G protein coupled receptors

have multiple helices that span
the plasma membrane and that
form hydrobhobic interactions
with the core of the plasma
membrane. G proteins bind to
the third and largest cytoplasmic
loop of the receptor.

Explain the process of G-protein activation using the diagram above:

11 | P a g e
When a ligand binds
to the binding site on
the receptor, the
receptor changes
shape, and induces a
shape change also in
the coupled G
protein. The G
protein is composed
of 3 subunits (𝛂, 𝛃
and 𝛄). The GDP
detaches from the 𝛂
subunit. This gives
place to GTP, which
results in the
activation of the G
protein.

An example of a g-protein receptor are opoid receptors – see the molecule of the month on the protein
database website: https://pdb101.rcsb.org/learn/paper-models/g-protein-coupled-receptor-gpcr

12 | P a g e
Mechanism of action of epinephrine (adrenaline) receptors:

Epinephrine (Adrenaline) is a hormone released from adrenal glands. It circulates in the blood
stream and binds to a class of G protein receptors (adrenergic receptors). It acts as a peptide
hormone which upon binding to the receptor activates a cascade of reactions mediated by a
secondary messenger to amplify the strength of the signal.

Effects of epinephrine:
• Preparation for vigorous activity
• Increase in heart- and breathing rate
• Enables increased delivery of oxygen and glucose to muscle cells.
• Vasoconstriction of blood vessels

cAMP is the most common

secondary messenger used in cells
and is activated by binding of
epinephrine to the G protein
coupled transmembrane receptor.

Use the diagram above to describe the mechanism of action in using epinephrine as a signalling chemical:

13 | P a g e
Transmembrane receptors with tyrosine kinase activity:

A kinase is an enzyme that adds a phosphate group from

ATP to a molecule to phosphorylate it.

Kinases are inactively bound to transmembrane

receptors. Upon bindng they become active and can
phosphorylate other molecules and trigger a chain of
reactions.

Some transmembrane
receptors are
composed of two
protein tails which are
tyrosine kinases. Upon
binding the kinases
move together to form
a dimer, and attach
phosphate groups to
the tyrosine parts. The
phosphorylation
triggers a chain of
reactions – typically
multiple of them.

Use the example of the insulin receptor shown below to explain how tyrosine kinase activation results in the
transport of glucose into a cell:

14 | P a g e
Intracellular receptors that affect gene expression:

Molecules which are hydrophobic are lipid-

soluble and can therefore simply diffuse
through the plasma membrane (e.g. steroid
hormones). Once inside the cell they can bind
to an intracellular receptor and move to the
nucleus where they affect gene expression by
regulating transcription.

Effects of the hormones oestradiol and progesterone on target cells:

The hormones oestradiol and progesterone are involved in

reproduction. They are steroid hormones and therefore lipid soluble,
so they can pass through the plasma membrane of target cells. Once
bound to a receptor within the cytoplasm the hormone-receptor
complex moves to the nucleus where it acts as a transcription factor
enhancing the transcription of specific proteins.

Do you remember the target cells and effects for the two hormones oestradiol and progesterone ?
Oestradiol Progesterone

Sources

Target
cells

Effects

15 | P a g e
Regulation of cell signalling pathways by positive and negative feedback:

Cell signalling can be Cell signaling can also be

positive, resulting in the end negative, resulting in an
product amplifying the increase of the end product
starting point so that more shutting off the start of the
product is created. signaling pathway so that
less is produced.

Positive feedback - example: Inositol triphosphate

Inositol triphosphate (IP3) is a (secondary) signalling
molecule required in many calcium dependent
processes. The binding of IP3 to a receptor causes a
release of Ca2+ ions from the endoplasmic reticulum.

The release of Ca2+ ions activates more IP3 receptors,

which consequently releases more ions.

Negative feedback - example: Insulin production

The use of insulin in the control of the blood sugar level is an example of negative feedback. Binding of insulin to
a transmembrane receptor leads to a signal cascade, which results in the expression of GLUT-4 membrane
protein containing vesicles. The membrane proteins are embedded within the membrane and allow absorption
of glucose. The decreased concentration of glucose in the blood inhibits insulin production.

16 | P a g e