cell signaling and communication
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Cell Signaling and Communication. Cell Signaling and Communication. Signals Receptors Signal Transduction Signal Effects: Changes in Cell Function Direct Intercellular Communication. Signals. - PowerPoint PPT PresentationTRANSCRIPT
15Cell Signaling
and Communication
15 Cell Signaling and Communication
• Signals
• Receptors
• Signal Transduction
• Signal Effects: Changes in Cell Function
• Direct Intercellular Communication
15 Signals
• Both prokaryotic and eukaryotic cells must process information from their environment and respond appropriately.
• Signals may be chemical molecules or physical stimuli such as light.
• Cells must be set up to interpret signals—not all cells can interpret all signals.
• To interpret a signal, a cell must have the appropriate receptor protein.
15 Signals
• Organisms receive many signals from the environment such as light, odors, tastes, temperature, touch, 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+.
15 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 diffuse to and affect nearby cells.
• When the target is distant, signals travel by circulation in the blood.
Figure 15.1 Chemical Signaling Systems (Part 1)
Figure 15.1 Chemical Signaling Systems (Part 2)
15 Signals
• The entire signaling process, from signal detection to final response, is called a signal transduction pathway.
• A signal transduction pathway involves a signal, a receptor, transduction, and effects.
• It is usually described as a series of events but many of the events are actually happening at the same time.
15 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.
15 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 transcription 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.
Figure 15.2 A Model Signal Transduction Pathway (Part 1)
Figure 15.2 A Model Signal Transduction Pathway (Part 2)
15 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.
15 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.
15 Receptors
• A ligand is the signaling molecule that binds the receptor.
• Binding of the ligand causes the receptor to change shape.
• The ligand has no further involvement in the pathway.
• Receptors bind ligands according to the law of mass action, and thus the binding is reversible.
Figure 15.3 A Signal Bound to Its Receptor
15 Receptors
• Inhibitors can bind to the ligand binding sites on receptor molecules.
• Natural and artificial inhibitors are important in medicine.
15 Receptors
• There are two classes of signaling molecules: Ligands with cytoplasmic 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.
Figure 15.4 Two Locations for Receptors
15 Receptors
• Three well-studied types of transmembrane receptors in complex eukaryotes:
Ion channel receptors
Protein kinases
G protein-linked receptors
15 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.
Figure 15.5 A Gated Ion Channel
15 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.
Figure 15.6 A Protein Kinase Receptor
15 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.
Figure 15.7 A G Protein-Linked Receptor (Part 1)
Figure 15.7 A G Protein-Linked Receptor (Part 2)
15 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, epinephrine causes the G protein to inhibit the production of cAMP, muscles relax, and the blood vessels open wide for maximum blood flow.
15 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.
Figure 15.8 A Cytoplasmic Receptor
15 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.
15 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.
Figure 15.9 A Protein Kinase Cascade
15 Signal Transduction
• There are at least three advantages to having many kinase steps in signal transduction:
Each activated protein kinase can phosphorylate many target proteins, so amplification 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.
15 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.
15 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.
Figure 15.10 The Formation of Cyclic AMP
15 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 second messengers, with IP3 moving into the cytoplasm and DAG remaining in the membrane.
• These second messengers trigger many cellular events.
Figure 15.11 The IP3 and DAG Second Messenger System
15 Signal Transduction
• Calcium ions are also second messengers.
• Ca2+ concentration in the cytoplasm is usually only about 0.1 M.
• 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.
15 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.
15 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.
15 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.
Figure 15.13 Nitric Oxide as a Second Messenger
15 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.
15 Signal Effects: Changes in Cell Function
• Signal effects may include:
The opening of membrane channels
Changes in enzyme activity
Differences in gene transcription
15 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.
Figure 15.14 A Signal Transduction Pathway Leads to the Opening of Ion Channels (Part 1)
Figure 15.14 A Signal Transduction Pathway Leads to the Opening of Ion Channels (Part 2)
15 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.
Figure 15.15 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 1)
Figure 15.15 A Cascade of Reactions Leads to Altered Enzyme Activity (Part 2)
15 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.
15 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.
15 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.
Figure 15.16 Gap Junctions Connect Animal Cells
15 Direct Intercellular Communication
• Plant cells communicate through plasmodesmata, 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.
Figure 15.17 Plasmodesmata Connect Plant Cells