CHAPTER 11 – CELL COMMUNICATION
YOU MUST KNOW:
 How external signals are converted into responses within the cell
 The processes of receptor binding and the various type of receptors
 The process of signal transduction with phosphorylation
 The role of second messengers in signal transduction
 The events of cellular response to various external signals
Start with doing the Pathways With Friends activity
I.
OVERVIEW:
 Cell-to-cell communication makes it possible to coordinate activities
among cells in multicellular organisms, but it is also important in
unicellular organisms.
 In this chapter we will focus on the main mechanisms by which cells
receive, process and respond to chemical signals sent from other cells.
Good site to watch:
http://www.ted.com/talks/bonnie_bassler_on_how_bacteri
a_communicate.html
II.
External Signals – Internal Responses
A. Evolution of Cell Signaling
 One type of cell signaling in Saccharomyces c. is used to identify their
mates. One mating type (a) releases a chemical a that binds to the
proper receptor of mating type , while it releases a factor  that binds to
a receptor of the a cell. These two cells will start to grow closer to each
other until they completely unite. This fusion will result in a new set of
genetic combinations from both organisms.


Changes inside of cells can be brought on by a signal transduction
pathway – the process by which a chemical signal on the surface of a
cell is converted into a specific cellular response inside the cell.
Molecular pathways of cell signaling are very similar in simple organisms
such as yeast and in more complex organisms such as humans. This
proves that these signaling mechanisms are very ancient and developed
early in evolution.
B. Local and Long-Distance Signaling
 Some signals directly affect neighboring cells (cell junctions and cell-cell
recognition) – direct communication

Local regulators – messenger molecules that are secreted by signal
cells and travel only to short distances by diffusion.
o Signals are released by certain cells and these cells are also
the ones that respond back to the signal – autocrine
signals
o Numerous surrounding cells can receive these signals and
respond to it. (Ex. Growth factors – make cells in the
vicinity grow and multiply) In animals this local signaling is
called paracrine signals.
o Synaptic signaling – is also a local signal type but it
occurs in the animal nervous system. An electrical signal
travels along the nerve cell and triggers the release of
specific chemicals called neurotransmitters. This signal
travels across a gap (synapse) between the neighboring cells
and stimulates the target cell.

Long-distance signaling affects specific target cells that are far away in
the body from the regulator cells. Examples:
o Endocrine cells – hormone releasing cells that release
hormones into the vessels of the circulatory system by which
they travel to the target cells. Plant hormones frequently
reach their target cells by moving from cell to cell or through
the air or soil.
o Transmission of nerve signals can also be considered longdistance signals when the long nerve cells carry the impulse
to various parts of the body and converts the electric signal
back to a chemical signal that crosses a synapse
C. The Three Stages of Cell Signaling
The entire signaling process – from the signal’s landing on a receptor to
conveying a message to the cytoplasm, the cell’s final response is called a
signal transduction pathway
 Reception – The target cell detects a signal molecule coming from
outside of the cell. The signal molecule must bind to a receptor molecule
on the cell’s surface or inside of the cell to be detected. The signal
molecule usually changes the shape of the receptor.
 Transduction – The binding of the signal molecule changes the receptor
protein and initiates the process of transduction – converting the signal to
a useful form that will generate changes in the cell.
 Response – A responder is the next component of the signal
transduction pathway. The responder is located inside of the cell and
responds to a change in the receptor by changing shape, forming new
bonds, releasing or binding with other molecules. The responder can
also:
Transfer phosphate groups from ATP to a target protein
Amplify a signal
Activate a transcription factor (a molecule that regulates mRNA
transcription)
Make a particular protein
Alter the cell’s activity
http://learn.genetics.utah.edu/content/begin/cells/cellcom/
III.
SIGNAL RECEPTION
 A receptor protein on or in the target cell will be able to detect the signal
molecule by a matching (complementary) shapes. The signal molecule
acts as a ligand by specifically binding to a specific molecule.
 Ligand binding usually causes a receptor to undergo conformation (shape)
change. This change usually directly activates the receptor to interact
with other molecules inside the cell. In some instances receptor binding
causes the aggregation of two or more receptors and causes further
cellular changes.
 Most receptors are protein molecules. Their ligands are large watersoluble molecules that cannot pass through the cell membrane easily.
However, some of the receptors are located inside the cell.
A. Intracellular Receptors:
 Intracellular receptor proteins are found inside the cytoplasm or in the
nucleus of the target cells. The signal molecules (ligands) in these cases
must be able to pass through the cell membrane to reach the receptor.
Signal molecules can do this by being hydrophobic or small to cross the
phospholipids bilayer. Examples of ligands that can pass through the cell
membrane includes steroids, thyroid, nitric oxide (NO).


The signal-receptor complex is able to regulate gene expression by acting
as a transcription factor that turns on specific genes. In cases of
receptors that get into the nucleus, the receptor and ligand complex can
carry out the entire reception and transduction process
Many of the intracellular receptor proteins have similar structures that
suggest their common evolutionary origin.
B. Receptors in The Plasma Membrane:
 Water-soluble signal molecules bind to receptor molecules on the surface
of the plasma membrane. These receptors have to change shape or
aggregate to perform transduction.
 Three major types of membrane receptors and their function:
 G-protein-linked receptor: these receptors are located in the
cytoplasm (integral proteins) and work with a G-protein (a group
of proteins that are made up of 3 subunits and are able to bind
with GTP and GDP). The G-protein has two important binding
sites. One site binds with the G protein-linked receptor, the other
binds with GDP in its inactive form and GTP, when the protein is
activated. Many different signal molecules can use G-protein linked
receptors (neurotransmitters, hormones such as epinephrine or
yeast mating factors). Many bacteria cause diseases by producing
toxins that intervene with G-protein function. These receptors
work the following way:
1. The G-protein acts as a molecular switch which is either on or off,
depending on which of the two guanine nucleotides is attached,
GDP or GTP. When GDP is attached to the protein, the protein is
inactive.
2. When a matching signal molecule binds to the receptor molecule,
the receptor is activated and changes shape. The change in shape
activates the G-protein, so it replaces its GDP with a GTP.
3. The activated G-protein dissociates from the receptor, moves to an
enzyme and alters it. When the enzyme is activated, it triggers a
cellular response.
4. The G protein changes back to its inactive form and returns to the
receptor molecule.
http://www.youtube.com/watch?v=bU4955rLv_8&feature=related

Protein Kinase Receptors – Once these receptors get activated,
they activate a group of enzymes, called protein kinases. Protein
kinases catalyze the transfer of phosphate groups from ATP to a
specific protein. This phosphorylation alter the shape of the target
protein and activates it. A good example of a protein kinase receptor
is an insulin receptor:
o The insulin receptor binds with insulin that comes from the
bloodstream.
o The receptor changes its shape after binding. This shape
change exposes the active site of a protein kinase in the
cytoplasm.
o Once the kinase is exposed, it phosphorylates several
cytoplasmic proteins.
o These proteins will expose a glucose transport protein to the
surface of the cytoplasm to make the cell absorb more glucose
and form glycogen from glucose in the cell.
Abnormal receptor tyrosine kinases that function in the absence of
signal molecules can contribute to some kinds of cancer.
http://www.youtube.com/watch?v=-iBb1sH-Eh4
 Ion channel receptors – a type of membrane receptors that can act
as a gate when the receptor changes shape. When the signal
molecule binds to the receptor protein, the gate opens or closes,
allowing or blocking the transfer of specific ions such as Na+ or Ca2+.
Each type of ion channel receptor has its ligand molecule (signal
molecule) or another sensory signal such as light, sound, electric
charge etc. (Ex. Acetylcholine receptors in nerve and muscle cells.
These receptors open up when acetylcholine binds with them and
allows Na+ ions to rush into the cell to generate a nerve signal or
muscle contruction).
IV.
TRANSDUCTION OF SIGNALS
 The same signal can produce a different response in different cells.
These responses are caused by the signal transduction.
 Signal transduction can be:
i. Direct transduction – transduction directly occurs with the
receptor on the plasma membrane
ii. Indirect transduction – a more common way when
another molecule called a second messenger mediates a
further interaction between the receptor and the cell’s
response.
Insert 15.9 from Life book here.


In both cases of transduction, a cascade of events is initiated by
the signal. During this cascade, proteins interact with each other
and/or change shape until the final responses are achieved.
Through the cascade, a weak signal can be amplified, or distributed
to cause several different changes in the target cell.
A. Transduction with protein kinases
Protein kinases for example act in direct transduction when the protein kinase
receptors expose the kinase enzymes to phosphorylate other proteins. These
are useful for creating cascades for the following reasons:
i. At each step of the cascade, the signal is amplified, because
the newly activated protein kinase is an enzyme which can
catalyze the phosphorylation of many target proteins
ii. The information that came from the original signal molecule
can be communicated all the way to the nucleus
iii. Depending on the presence of various enzymes, this
response can become very specific.
iv. Protein kinases can easily be deactivated by another enzyme
called protein phosphatase that cuts off the phosphate
group from the protein and deactivates it.
B. Transduction with second messengers
 Many signaling pathways also involve small water-soluble molecules or
ions – second messengers. These result in indirect signal transduction.
 Second messengers are molecules that are released into the cytoplasm
after the first messenger (the signal) binds to its receptor. The second
messenger affects many processes in the cell, so one single signal
molecule can result in widespread changes in the cell.
 Second messenger can also amplify signals.
 Second messengers are nonprotein molecules, so they do not act as
enzymes but act as cofactors or allosteric regulators of target enzymes.
 Different types of second messengers:
o Cyclic AMP – An enzyme called adenylyl cyclase, is embedded
in the plasma membrane to convert ATP to cAMP in response to an
extracellular signal (ex. Epinephrine). When the signal molecule
binds to a receptor, the receptor activates adenylyl cyclase to form
many molecules of cAMP. This way one signal molecule can induce
the synthesis of many cAMP molecules. The cAMP molecule usually
activates a protein kinase molecule to phosphorylate various
proteins. Once the cAMP activated a protein kinase molecule the
cAMP is converted back to AMP by another enzyme called
phosphodiesterase. Many diseases are caused by toxins that
interact with the second messenger system (ex. Cholera)
o Ca2+ ions – Many signal molecules, including neurotransmitters,
growth factors, some hormones induce responses that increase the
cytosolic concentration of calcium ions. Increased calcium ion
concentration can cause muscle contraction, secretion of certain
substances or cell division. This system can work because the
normal Ca2+ ion concentration in the cytosol is a lot lower than in
the smooth ER or in the extracellular matrix. A small change in the
absolute concentration can result in a substantial change in the
cytosol. The release of Ca ions involves the activation of other
second messengers such as inositol triphosphate (IP3). The
activated IP3 will move to the endoplasmic reticulum and will
activate transport proteins to release stored calcium ions into the
cytosol. A good example of Ca2+ as a second messenger is when
the sperm cell unites with the egg, results in a massive release of
Ca ions into the egg cytoplasm that starts the various changes that
leads to the development of the embryo.
o Nitric oxide (NO) – this very unstable gas that can act as a short
term, short distance second messenger that is usually activated by
Ca ions. NO generally result in muscle relaxation that is important
when increased blood flow is required.
V.
RESPONSE TO SIGNALS
A. Cytoplasmic and Nuclear Responses
 The response of the cell to various signals may occur in the cytoplasm or
in the nucleus.
 If it occurs in the cytoplasm, it may result in the opening or closing of ion
channels or a change in cell metabolism.
 If this response occurs in the nucleus, it usually triggers the transcription
and translation of various enzyme molecules by turning the appropriate
genes on. In some cases the response can turn certain genes off that
have been active previously.
B. Fine-Tuning of the Response:
 Signaling pathways usually have a large number of steps between the
signal-receptor activation and the cell’s response. The reason for this is
that the signal can be amplified (few signal molecules can trigger
substantial changes in the cell) and the response can be very specific for a
wide variety of cells (this is possible because various cells will have
various proteins so the same signal molecule can trigger a wide range of
responses depending on what proteins are present in any given cell)
C. Termination of the Signal
 Each molecular change that a cell receives only lasts for a short time. The
signal molecules can easily detach from the receptor and the receptor
turns back into its inactive state quickly. The relay molecules also return
to their inactive form quickly with the help of various enzymes.
Watch this at the end: http://www.dnalc.org/resources/3d/index.html
AS A REVIEW – DO MY DOG IS BROKEN – CASE STUDY
END OF UNIT