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 signal-transduction 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. Paracine 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
1. Reception
2. Transduction
3. Response1. 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, neurotransmittors 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. NoteBacteria 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 receptorsSome 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 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