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15 Announcements
• Deadline for Online Quiz 14 – Not Midnight Tonight. Residence Halls are experiencing internet access problems; InfoTech expects a solution by the end of today. New deadline: Wednesday @ midnight.
• Some driving advice: Although you may be able to see the road, others may not be able to see you. To avoid a senseless accident, turn your headlights on when daylight is limited or when it’s raining.
http://www.the-instructor.com/eyes.jpg
15Cell Signaling
and Communication
15 A Bit Tired
Studying for BIO 121?
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15 Adenosine Receptors in the Brain & Elsewhere
Caffeine attached to adenosine receptor
http://userpage.chemie.fu-berlin.de/~schalley/grafiken/sigroesm.jpg
http://userpage.chemie.fu-berlin.de/~schalley/grafiken/sigroesm.jpg
Adenosine Compare with
caffeine.
http://www.worldofmolecules.com/life/150px-Adenosine.png
15 Blame Adenosine
• A tired person’s brain produces adenosine
molecules that bind to specific receptor proteins,
resulting in decreased brain activity and increased
drowsiness. Caffeine’s molecular structure is similar
to that of adenosine, so it occupies the adenosine
receptors without inhibiting brain cell function, and alertness is restored.
- Purves et al.http://www.studeren.uva.nl/cache/1CEFE26B-257F-4352-B98B23886495B772.FOTO.jpg
15 Cell Signaling and Communication
How do cells respond to signals in their environment?
• 1. The signal binds to a receptor protein in the cell, often on the outside surface of the plasma membrane.
• 2. The binding of the signal causes a message to be conveyed to the inside of the cell and amplified.
• 3. The cell changes its activity in response to the signal. - Purves et al.
15 Signals
Some Facts to Consider
1. Both prokaryotic and eukaryotic cells must process information from their environment and respond appropriately.
2. Signals may be chemical molecules or physical stimuli such as light.
3. Cells must be set up to interpret signals—not all cells can interpret all signals.
4. To interpret a signal, a cell must have the appropriate receptor protein.
5. Organisms receive many signals from the environment such as light, odors, tastes, temperature, touch, and sound.
15 Signals
6. Multicellular organisms’ internal cells are exposed to extracellular fluids and other cells, from which they receive information.
7. A few of the many types of signals in animal cells are hormones, neurotransmitters, chemical messages from the immune system, CO2, and H+.
http://www.ebi.ac.uk/interpro/potm/2004_4/Page2_files/image002.gif
15 Target Cells
Target & Non-Target Cells
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.
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 (transfers a phosphate group from ATP), 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.
Cartoon above:http://www.kumc.edu/instruction/medicine/microbio/lutkenhaus/cartoon2.gif
15 Signals
…continued
• 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)
15 Layered Figure
• Layered Figure 15.2: A Model Signal Transduction Pathway
Figure 15.2 A Model Signal Transduction Pathway (Part 2)
15 Signals
• A review of the steps in this signal transduction pathway (and many others):
A receptor (EnvZ) binds with the signal molecule (solute) and changes shape.
Conformational change (in EnvZ) results in kinase activity (ability to transfer phosphate groups).
Phosphorylation (EnvZ phosphorylates itself) alters the functioning of a protein.
The signal is amplified (one EnvZ molecule alters the structure of many OmpR molecules).
Transcription factors are activated (phosphorylated OmpR).
Altered synthesis of specific proteins (OmpC) occurs.
Protein action alters cell activity (pores blocked).
15 Receptors
RECEPTORS• Because receptors are essential in a signal transduction
pathway, a cell responds to only a few of the many signals it receives.
• The type of receptors each cell makes is genetically determined. Recall that receptors are proteins and that different cells express different sets of genes (genes turned on).
15 Receptors
• Receptors have specific binding sites for their signals.
• 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, in fact, in many cases the ligand serves no purpose other than to “knock on the door.”
• Receptors bind ligands according to the law of mass action, and thus the binding is reversible… (next slide) http://www.ebi.ac.uk/interpro/potm
/2004_4/Page2_files/image002.gif
15 Law of Mass Action
If the ligand binds permanently to the receptor, the receptor would be continuously stimulated. Not good!
Reversible reactionhttp://www.graphpad.com/curvefit/law_of_mass_action.htm
GH schematic (modified)http://www.ebi.ac.uk/interpro/potm/2004_4/Page2_files/image002.gif
Reversible!
Why is this important? Control
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. For example, many of the drugs that alter human behavior bind to specific receptors in the brain.
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 (e.g., estrogen).
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 Announcements
• Online Quiz 14 Deadline Tonight (no need to extend further because of internet problems)
• Beta Beta Beta and the Biology Club are cosponsoring a “Career Night” tomorrow (Thursday), 7 PM, TCC1867. Alumnae and scientists will be discussing career opportunities.
• Open Lecture Thursday: Come if you’re interested in the topic. Dr. Reyna Favis (from Johnson & Johnson), OBC1, Thursday 4PM. Pharmacogenomics in Clinical Trials: Innovation in a Regulated Environment
For special lectures such as the one above, do not enter the room after the lecture begins, and do not leave until the lecture is over. If you cannot attend the full lecture (~60
min), do not attend. Thank you.
15 Receptors
Recall: There are three well-studied types of transmembrane receptors in complex eukaryotes:
Ion channel receptors (e.g., acetylcholine and sodium channels)
Protein kinases (e.g., solutes and EnvZ protein; also insulin and insulin receptor)
G protein-linked receptors (e.g., epinephrine and G protein receptor)
Figure 15.5 A Gated Ion Channel
Figure 15.6 A Protein Kinase Receptor
Figure 15.7 A G Protein-Linked Receptor (Part 1)
Figure 15.7 A G Protein-Linked Receptor (Part 2)
Figure 15.4 Two Locations for Receptors
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.
Steroid hormones are small and hydrophobic, and most hormones of this class are derived from cholesterol, including estrogen, progesterone, testosterone, and cortisol. Since they are small and hydrophobic, they can diffuse through the cell membrane. These hormones bind steriod hormone receptors after they have diffused into the cell through the plasma membrane. The hormone bound receptors enter the nucleus and bind to target regions in genes that regulate transcription, turning the genes on or off. Steroid hormone signals are changes in gene transcription and protein expression caused by the steroid hormone receptors. http://trc.ucdavis.edu/biosci10v/bis10v/week10/
Figure 15.8 A Cytoplasmic Receptor
15 Signal Transduction
Moving on from the receptors to:
Signal Transduction
“step” 2 of a signal transduction pathway
15 Variable Responses
“…the same signal may produce different responses in different tissues. When epinephrine, for example, binds to receptors on heart muscle cells, it stimulates muscle contraction, but when it binds to receptors on smooth muscle cells in the blood vessels of the digestive system, it slows muscle contraction. These different responses to the same signal-receptor complex are mediated by the events of signal transduction.” -Purves et al.
http://cellbio.utmb.edu/microanatomy/muscle/muscle12.jpghttp://wappingersschools.org/RCK/staff/teacherhp/johnson/visualvocab/Smooth%20muscle.jpg
cardiac muscle smooth muscle
15 Signal Transduction
The events of signal transduction can be either direct or indirect:
• 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. Examples of second messengers: cyclic AMP (cAMP), DAG, IP3, nitric oxide (NO). Second messengers are not enzymes, instead they act as cofactors or allosteric regulators of target proteins.
• In both direct and indirect transduction the signal initiates a series of events that eventually lead to a final response.
Figure 15.9 A Protein Kinase Cascade
Figure 15.13 Nitric Oxide as a Second Messenger
15 Signal Effects: Changes in Cell Function
Time for “step” 3:
Signal Effects:
Changes in Cell Function
15 Typical Effects
Typical effects fall into three categories:- Opening of Ion Channels- Changes in the Activities of
Enzymes- Differential Gene Transcription
15 Signal Effects: Changes in Cell Function
AN EXAMPLE: SENSE OF SMELL
• 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 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
