Cell Signaling
and Communication
Signals
Receptors
Signal Transduction
Signal Effects: Changes in Cell Function
Direct Intercellular Communication
Signals
Both prokaryotic and eukaryotic cells must process ________ from their
environment and respond appropriately.
Signals may be chemical molecules or physical stimuli such as light.
Cells must be set up to interpret signalsnot all cells can interpret all
signals.
To interpret a signal, a cell must have the appropriate receptor protein.
Signals
Organisms receive many signals from the environment such as ________ ________
________ temperature, ________ and sound.
Multicellular organisms' internal cells are exposed to extracellular fluids
and other cells, from which they receive information.
A few of the many types of signals in animal cells are hormones,
neurotransmitters, chemical messages from the immune system, CO2, and H+.
Signals
In large animals, signals reach targets via diffusion as autocrine or
paracrine signals when the target is close.
Autocrine signals are signals generated by the same cells upon which they act.
Paracrine signals ________ to and affect nearby cells.
When the target is distant, signals travel by circulation in the blood.
Signals
The entire signaling process, from signal detection to final response, is
called a signal ________ pathway.
A signal transduction pathway involves a signal, a receptor, ________ and
effects.
It is usually described as a series of events but many of the events are
actually happening at the same time.
Signals
An example using E. coli:
The signal is rising solute concentration outside the cell.
The receptor protein is EnvZ, a transmembrane protein. Rising solute
concentration changes the protein's conformation.
EnvZ becomes a kinase, and phosphorylates itself.
A responder is the second component in the pathway. EnvZ now binds to OmpR,
which takes the phospate group. OmpR changes shape.
Signals
The signal on the outside of the cell has been transduced to a protein inside
the cell, the phosphorylated OmpR.
Phosphorylated OmpR is a ________ factor. It binds to the promoter for the
ompC gene.
The protein OmpC is inserted into the outer membrane where it blocks pores and
prevents solutes from entering.
Signals
A review of the steps in this signal transduction pathway:
§ A receptor binds with the signal molecule and changes shape.
§ Conformational change results in kinase activity.
§ Phosphorylation alters the functioning of a protein.
§ The signal is amplified.
§ Transcription factors are activated.
§ Altered synthesis of specific proteins occurs.
§ Protein action alters cell activity.
Receptors
A cell responds to only a few of the many signals it receives.
The type of receptors each cell makes is genetically determined.
Receptors have specific binding sites for their signals.
Receptors
A ________ is the signaling molecule that binds the receptor.
Binding of the ________ causes the receptor to change shape.
The ________ has no further involvement in the pathway.
Receptors bind ligands according to the law of mass action, and thus the
binding is reversible.
Receptors
Inhibitors can bind to the ligand binding sites on receptor molecules.
Natural and artificial inhibitors are important in medicine.
Receptors
There are two classes of signaling molecules:
§ Ligands with ________ receptors: small and/or nonpolar molecules that can
cross the plasma membrane, such as steroids.
§ Ligands with plasma membrane receptors: large and/or polar molecules that can
not cross, such as insulin. Receptors are usually transmembrane proteins.
Receptors
Three well-studied types of transmembrane receptors in complex eukaryotes:
§ Ion channel receptors
§ Protein kinases
§ G protein-linked receptors
Receptors
Some ion channel proteins, acting as "gates," are signal receptors.
Channel proteins can open to let certain ions in or out, or close to restrict
them.
The signal to open or close the channel can be chemical, light, sound,
pressure, or voltage.
An example of a gated ion channel is the acetylcholine receptor.
Receptors
Some eukaryotic receptor proteins become kinases when activated.
A phosphate is transferred from ATP to a protein, the target protein, changing
its shape or activity.
Sometimes the protein kinase phosphorylates itself. This is called
autophosphorylation.
Insulin receptors are examples of protein kinase receptors.
Receptors
The seven-spanning G protein-linked receptors are proteins with seven regions
that pass through the lipid bilayer.
A ligand binds to the extracellular side and changes the shape of the protein
on the cytoplasmic side. This exposes a binding site for the G protein.
G protein also has a binding site for GTP. The GTP-bound subunit separates and
moves along the membrane until it finds an effector protein.
The effector protein may catalyze many reactions, amplifying the signal.
Receptors
G proteins can either activate or inhibit effectors. Epinephrine illustrates
both possibilities.
In the heart, epinephrine causes the G protein to activate an enzyme that
produces cAMP, which has a wide range of effects on the cell.
In smooth muscle cells around blood vessels, ________ causes the G protein to
inhibit the production of cAMP, muscles relax, and the blood vessels open wide
for maximum blood flow.
Receptors
Cytoplasmic receptors which are located inside the cell bind with ligands that
can cross the plasma membrane.
The receptor changes shape and can then enter the nucleus where it acts as a
transcription factor.
Steroid hormones are an example of such signal molecules.
Signal Transduction
Transducers convert signals from one form to another.
Direct transduction results from the action of the receptor itself on effector
proteins. Direct transduction occurs at the plasma membrane.
Indirect transduction uses a second messenger to mediate the interaction
between receptor binding and cellular reaction.
In both direct and indirect transduction the signal initiates a series of
events that eventually lead to a final response.
Signal Transduction
A protein kinase cascade is direct signal transduction that catalyzes the
phosphorylation of target proteins.
Details of a certain protein kinase cascade were discovered from the
investigation of Ras protein inhibition as treatment for bladder cancer.
Ras is part of a protein kinase cascade that influences cell division. The
pathway is called a cascade because each kinase phosphorylates the next.
Signal Transduction
There are at least three advantages to having many kinase steps in signal
transduction:
§ Each activated protein kinase can ________ many target proteins, so ________
of the signal occurs at each step.
§ A signal at the cell membrane is transferred to the nucleus.
§ Having many steps affecting different target proteins allows for a variety of
responses by different cells to the same signal.
Signal Transduction
Indirect transduction is more common than direct transduction.
Scientists investigating the effects of epinephrine on the liver enzyme
phosphorylase discovered cyclic AMP (cAMP) as a second messenger.
The second messenger carries the signal from the membrane receptor to the
cytoplasm.
Second messengers affect many cell processes, amplifying the signal.
Signal Transduction
The cAMP molecule is a small cyclic nucleotide generated from ATP.
The enzyme adenylyl cyclase produces cAMP using ATP as a substrate. Adenylyl
cyclase is activated by an activated G protein subunit.
Like other second messengers, cAMP is not an enzyme. Second messengers act as
cofactors or allosteric regulators of target proteins.
cAMP has two major kinds of targets: ion channels and protein kinases.
Signal Transduction
Phospholipids can be hydrolyzed into components that act as second messengers.
Phosphatidyl inositol-bisphosphate (PIP2) is hydrolyzed into inositol
triphosphate (IP3) and diacylglycerol (DAG).
The two parts each become ________ messengers, with IP3 moving into the
cytoplasm and DAG remaining in the membrane.
These second messengers trigger many cellular events.
Signal Transduction
Calcium ions are also second messengers.
Ca2+ concentration in the cytoplasm is usually only about 0.1 mM.
The concentration is kept low via active transport, both out of the cell and
into the ER.
Unlike cAMP, Ca2+ cannot be manufactured in the cell; it must be imported.
Many different signals cause Ca2+ channels to open, including IP3.
Signal Transduction
Once a signal triggers Ca2+ channels to open, Ca2+ concentration rapidly rises
to 100 times the resting concentration.
The calcium ions then affect the activities of cellular proteins, including
protein kinase C.
Ca2+ also binds to Ca2+ channel proteins, triggering additional releases of
Ca2+.
Calcium ions bind to a calcium-binding protein called calmodulin, which can
activate certain proteins.
Signal Transduction
The gas nitric oxide (NO) was found to be a second messenger by scientists
studying the effects of acetylcholine, which causes the relaxation of smooth
muscles of the blood vessels.
Acetylcholine stimulates the IP3 pathway to produce an influx of Ca2+, which
leads to an increase in the level of another second messenger, cGMP.
This messenger stimulates a kinase cascade leading to muscle relaxation.
Signal Transduction
However, the pathway does not work in isolated artery tissue, which lacks an
endothelial lining.
It was discovered that NO, produced by the endothelial cells, was also needed.
Acetylcholine causes increased Ca2+ levels in the endothelial cells, which
causes the activation of NO synthase, the enzyme that makes NO.
NO diffuses rapidly from the endothelial cells to the nearby smooth muscle
cells.
In the smooth muscle cells, NO activates the enzyme guanylyl cyclase, which
stimulates the formation of cGMP.
Signal Transduction
Cells must regulate the activity of transducers.
NO is unstable and breaks down quickly, so NO is regulated by how much of it
is made.
Ca2+ concentrations are restored by mechanisms such as membrane pumps and ion
channels.
Protein kinase cascades are interrupted by protein phosphatases that remove
the added phosphates, deactivating the kinases.
GTPases deactivate G proteins by converting GTP to GDP.
Both cAMP and cGMP are converted to AMP and GMP by their respective
phosphodiesterases.
Signal Effects: Changes in Cell Function
Signal effects may include:
§ The opening of membrane channels
§ Changes in enzyme activity
§ Differences in gene transcription
Signal Effects: Changes in Cell Function
Sensory nerve cells of the sense organs are stimulated through the opening of
ion channels.
Each of the thousands of nerve cells in the nose expresses just one of these
receptors.
When an odorant molecule binds to its receptor, a G protein becomes activated,
which leads to formation of the second messenger, cAMP.
The cAMP binds to ion channels, causing them to let in Na+.
The change in Na+ ion concentration stimulates the neuron to send a signal to
the brain.
Signal Effects: Changes in Cell Function
The effects of epinephrine on liver cells results in altered enzyme activity.
The binding of epinephrine to a G protein-linked receptor results in synthesis
of cAMP, which in turn initiates a series of kinase reactions.
Two enzymes are altered:
§ Glycogen synthase is deactivated by phosphorylation.
§ Glycogen phosphorylase is activated, catalyzing the release of glucose
molecules from glycogen.
Signal Effects: Changes in Cell Function
Plasma membrane receptors are involved in initiating a broad range of gene
expression responses.
Ras signaling pathways end in the nucleus where genes involved in cell
division are transcribed.
Steroid hormones bind to receptors in the cytoplasm, which then influence gene
transcription.
In plants, light activates phytochrome, which then binds to cytoplasmic
regulatory proteins. These then move to the nucleus and influence genes that
lead to synthesis of chloroplasts.
Direct Intercellular Communication
Some cells send signals directly from their interior to the interior of
adjacent cells.
This transfer occurs by way of specialized structures called gap junctions in
animal cells, and plasmodesmata in plant cells.
Direct Intercellular Communication
Gap junctions permit metabolic cooperation among linked animal cells.
Gap junctions are complexes of proteins that make channels, called connexons
in adjacent cell membranes.
The channel is large enough for small signal molecules and ions to pass.
Signal molecules such as hormones and second messengers such as cAMP and PIP2
also can move through gap junctions.
Direct Intercellular Communication
Plant cells communicate through ________ membrane-lined channels spanning the
thick cell walls between adjacent cells.
A tube called the desmotubule fills most of the channel; generally only small
molecules move through.
Plasmodesmata are important to C4 plants, helping them to move fixed carbon
between mesophyll and bundle sheath cells.
Plasmodesmata pore size can be regulated.
Video 15.1 Chemotaxis of human neutrophils
Video 15.2 Calcium waves in brain glial cells
Animation 15.1 Signal Transduction Pathway