Cell-to-cell signaling is important to both
multicellular organims and unicelluar
organisms. It helps to coordinate the
activities and events necessary for a
multicellular organism to develop from a
zygote to into billion of cells. In unicellular
organisms signaling is important in finding
different mating types for sexual
reproduction. Yeast cells have two distinct
mating types- “a cells” and “alpha cells”. “a
type cells” secrete a chemical called “a
factor” and called “alpha factor”. The both
of these cells have receptor sites for each others factors. Once each cell receives the
other mating factors, these mating factors
cause the cells to grow toward one another
and bring about other changes. Inside the
cells there are a series of chemical changes
that cause the response. This series of
chemical events that occur is called the signaltransduction path way. The new a/alpha cell
has all the genes from both the different
haploid yeast cells. These pathways are
common to both humans and yeast cells
suggesting that this strategy evolved very early
on. These pathways are common to both
humans and yeast cells suggesting that this
strategy evolved very early on. Communication between cells can very close (local
signaling) or some distance away (hormonal and pheromone) signaling.
Local signalinga. Paracrine signaling-involves a cell secreting a chemical that acts on nearby
target cells. i.e. A cell may release a growth factor that may cause surrounding cells to
grow and multiply.
b. Neurons secrete
neurotransmitters
that diffuse across an
intercellular space
(synapse) and
interacts with a
another neuron.
Note-Local signaling in
plants is not as well
understood because of
the plant cell wall,
plant must use a
different mechanism than those operating in animals.
Long distance signalinga. Use of hormones (is a chemical secreted by one cell but exerts is effect on another
cell some distance away). In animals the hormone is released into the vessels of
circulatory system and the molecules travel to target cells. In plant cells, the hormones
may travel in vessels or diffuse the the air as a gas. Hormones may vary in their size
and molecular structure.
Types of Animal Hormones
Modified amino acids- i.e. epiniphrine is a modified tyrosine.
Proteins-i.e. insulin is a large protein
Steroid Hormones- i.e. testoterone and estrogen are
steroids.
b. Pheromones are chemicals secreted by one animal to
affect the behavior of another animal.
Direct contact- Cells have cell junctions which is in
contact of the cytoplasms of adjacent cells occur. This
allows for signaling substances in the cytosol to pass feely
between the adjacent cells. Animals cells can communicate
via direct contact between molecule on their surface of their
cell membranes. This is common in embryonic development
and the immune system (secretion of interleukin when macrophage and virgin-T cell
make a match).
The three stages of cell signaling are(**know these**)
1. Reception
2. Transduction
3. Response
1. Reception- A large portion of the reception of a signal begins with the signal
interacting with a receptor site
located on the outside surface of
the plasma membrane and will
never enter the cell itself. Quite
often the signal is a ligand (a small
molecule that attaches to a large
one). When the ligand attaches it
will cause a change in the shape of
the receptor site. Receptors are
usually proteins inserted into the
plasma membrane.
Three major types of membrane receptors are
a. G-protein-linked receptors
b. tyrosine-kinase receptors
c. ion-channel receptors
a. G-protein-linked receptors vary in their binding sites and
for recognizing different G-proteins. Most have seven alpha
helices penetrating the plasma membrane. When a G-protein-linked
receptor binds with a signal or ligand, it
becomes activated and interacts with a
G-protein. Yeast mating factors,
epinephrine, neurotransmitters and
other hormones use G-protein-linked
receptors. G-protein-linked receptors
activate G proteins. G proteins are
also found in the plasma membrane.
They are activated when the G-proteinlinked receptors causes GTP to replace
GDP on the G-protein.
Once this happens the activated Gprotein now moves laterally to interact
with a given enzyme also located in the
plasma membrane which causes a
certain biochemical pathway to be
activated. Once this occurs, the Gprotein cleaves a phosphate group
from GTP and makes it GDP and thus
the G-protein becomes inactivated.
These biochemical pathways include developmental pathways, sensory perception in
vision and smell. Note-Bacteria that often cause disease by secreting toxins. These
toxins may interfere with G-protein functions. 60% of all medicines exert their effect by
influencing G-protein pathways.
b. Tyrosine-Kinase receptors-are receptors that when activated can activate more than
one signal-transduction pathway at one time. This is important when an event like cell
reproduction requires a number of biochemical pathways to be activated at once. The
tyrosine-kinase receptor in the inactive form is two separate polypeptide chains forming
alpha helices that span the membrane. Inside the cell, the two polypeptides have
tyrosines on tails that extend into the cytoplasm. Both have a receptor site for a signal
or ligand. Once both receptors are activated, the polypeptides move toward one
another and bond with one another to form a dimer.
Now the dimer is phosphorylated at every tyrosine by ATP. Now the receptor is
activated and can trigger with a number of transduction-signal pathways. This may
include the transfer of a phosphate to another enzyme. Triggering a number of these
pathway is the main difference bewteen this receptor and the G-protein-linked receptor.
c. Ligand-gated ion channels. These channels are protein pores on the plasma
membrane that open or close in response to a chemical signal allowing or preventing
the flow of ions into or out of the cell. Examples include Na+ or Ca++. Once the signal
attaches to the gated channel, the protein changes shape and a pore opens. This
allows for an immediate change in the concentration of ions.
d. Intercelluar receptors-Some signal receptors are NOT found in the plasma
membrane. Instead they are dissolved in the
cytoplasm. This means the signal must be lipid
soluble to make into the cytosol. These signals
are usually steroids hormones, thyroxine, and
nitric oxide. i.e. Testosterone enters the cell and
binds with a receptor protein found in the
cytoplasm. This complex now moves to the
nucleus where is acts a transcription factor and
helps transcribes certain genes.
Transduction-After reception, the cell needs to
process the signal. This is called tranduction
and is a mult-step process. Usually the
molecules that are processing the signal are
proteins that are activated by phophorylating them. Protein kinases are proteins that
transfer phosphate groups from ATP to another protein. Serine and threonine of the two
amino acids that receive the phosphate group on the receiving protein.
A biochemical pathway usually has a cascading effect where one protein kinase will
activate another protein kinase by transferring a phosphate group on to it. These
protein kinases are extremely important. Approximately 1% of all our genes code for
various protein kinases. Protein phosphatase is a protein that will remove a phosphate
group from proteins and can deactivate a protein kinase. Between the receptor
molecule that is activated and signal-transduction pathway that is to be activated there
may be a second messenger. Note-The hormone or signal that attaches the to the
receptor site is called the first messenger. The most common secondary messengers
include
a. cyclic AMP
(cAMP)
b. Calcium ions and
inositol
triphosphate.
cAMP-i.e. When
epinephrine binds to its receptor site, it is
found that there is a corresponding
increase in the amound of cAMP found in
the cell. cAMP is a derivative of ATP. An
enzyme (adenlate cylase) in the plasma
membrane causes this reaction to occur. In
this example, epinephrine activates a
receptor site, which in turns activates the Gprotein. The G protein now activates
adenlyate cyclase, which then makes cAMP
from ATP. cAMP activates the epinephrine
pathway which ultimately increases the
amount of glucose in the blood stream.
Calcium ions and Inositol Triphosphate (IP3)
Some signal molecules in animals induce responses by increasing the amount of Ca++
in the cytosol. This is used in the muscles and nerves and certain hormones. Most of
the time Ca++ in the cytosol is low because it is pumped into the E.R., the mitochondria
and also outside of the cell. The release of Ca++ from E.R.
reservoirs involves diacylglycerol (D.A.G.) and inositol
triphosphate (IP3). These two messengers are made by the
cleavage of certain kind phospholipid in the plasma membrane.
This is done when the G protein acitvates an enzyme
phospholipase C. Phospholipase C cleaves a plasma
membrane in two to make D.A.G. and IP3. IP3 will then move
to the E.R. and bind with a IP3-gated calcium channel to allow
Ca++ to flow out.
Types of cellular
responses
1. Ultimately
activating an enzyme
2. Synthesis of a
particular enzyme or
protein
1. Activating an
enzymeUsually when cAMP,
Ca++ or IP3 is
activated then it will
interact with a specific enzyme to start the cascading effect
•Scaffolding proteins are large relay proteins to which other relay proteins are attached
•Scaffolding proteins can increase the signal transduction efficiency by grouping
together different proteins involved in the same pathway
Termination of signal
•Inactivation mechanisms are an essential aspect of cell signaling
•When signal molecules leave the receptor, the receptor reverts to its inactive state
Chapter 11 – Cell Communication – Homework
1. Identify and describe the three stages of cell signaling.
2. Discuss what determines whether a cell is a target cell for a particular signal molecule.
3. Explain why most signals cannot cross the cell membrane and discuss the similarity between
these reasons and why these reasons molecules need active transport mechanisms.
4. Describe what is a phosphorylation cascade.
5. Discuss what general properties molecules that function as secondary messengers have in
common.
6. Discuss why cell signaling is an important component of a
cell’s life.
7. Discussr why apoptosis is necessary and even useful.