1. CELL Communication
Chapter 11

2. OUTLINE An overview of Cell signaling
A. Cell signaling evolved early in the history of life
B. Communicating cells may be close or far apart
C. Three stages of cell signaling are: reception, transduction, response

3. OUTLINE II II. Signal reception and the Initiation of Transduction
A. A chemical receptor binds to a receptor protein, causing the receptor protein to change shape
B. Most signal receptors are plasma-membrane proteins

4. OUTLINE III III. Signal Transduction Pathways
A. Pathways relay signals from receptors to cellular responses
B. Protein Phosphorylation is a major mechanism of signal transduction
C. Certain small molecules and ions are key components of signaling pathways (second messengers)

5. OUTLINE IV IV. Cellular Responses to Signals
A. In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus.
B. Elaborate pathways amplify and specify the cell’s responses to signals

6. Cell Signaling Evolved Early
Yeast mating is coordinated by chemical signaling
Yeast have 2 mating types, a and alpha
Type a cells secrete a-factor chemical signal, alpha cells secrete alpha factor
The binding of a-factor to alpha cells and vice versa causes cells to move toward each other and fuse

7. Yeast tie ins
The steps by which yeast mating signals are converted into cell responses are similar to how prokaryotes, plants, animals chemical signals are converted to specific cell responses
The Steps by which a chemical signal is converted into a cell response is called a signal transduction pathway

8. Yeast Communication

9. Communicating cells may be close or far
LOCAL REGULATOR: a chemical signal which communicates between 2 nearby cells
PARACRINE SIGNALING: a cell secretes the signal into extracellular fluid, acts on nearby cell
SYNAPTIC SIGNALING: a nerve cell releases a signal (ie. neurotransmitter) into a synapse. The target cells are other nerve cells or muscle cells

10. Distance makes the heart grow fonder….
HORMONES: signal to cells which are some distance apart
Examples: Ethylene in plants, insulin in animals

11. Local and Distant Cell Communication

12. Direct Contact
Some animal and plant cells can communicate directly through junctions through which signals can travel between adjacent cells.

13. Communication By Direct Contact

14. Reception, Transduction, Response
In order for the signal to cause a response in a cell, that cell must have the proper signaling system. Cells without ignore the signal.
RECEPTION: the signal binds to a specific cellular protein called a receptor, usually on the cell’s surface
SIGNAL TRANSDUCTION: the binding causes a change in conformation, which then converts the signal into a cell response
CELLULAR RESPONSE: the transduction system causes a specific cell response, ie. Altered gene expression, enzyme activation

15. Signal Reception and the Initiation of Transduction
A chemical signal binds to a receptor protein causing the protein to change shape
The signal is complementary to the receptor protein (like an active site)
The signal behaves as a LIGAND: A small molecule that binds to a larger one. This binding can lead to:
Change in protein conformation, allowing it to interact w/other cell molecules
Aggregation of receptor complexes

16. Overview of Cell Signaling

17. Most Signal Receptors are Plasma-membrane proteins
3 Types:
G-Protein-Linked Receptors
Tyrosine-Kinase Receptors
Ion-channel receptors

18. G-Protein-Linked Receptors
Weaves in and out of the membrane 7 times (has 7 transmembrane domains)
Example: Epinephrine receptor
The receptor causes a response by interacting with proteins on the cytoplasmic side called G-proteins, cause they bind Guanine nucleotides, GDP, GTP
G proteins bound to GDP: Inactive
G proteins bound to GTP: Active

19. Yo, G (protein)
When a ligand binds to a G-Protein-Receptor, the conformation changes and reacts with a G-protein, which causes the GDP to be displaced by GTP, thus activating it.
The activated G protein binds to another protein, usually an enzyme, resulting in the activation of a target enzyme.
This is temporary, as the G-protein has GTP-ase, which breaks it back down to GDP

20. The functioning of a G-Protein

21. G-Protein Structure

22. Tyrosine-Kinase Receptors
2 Parts: 1. Extracellular ligand-binding domain, 2. cytosolic domain posessing tyrosine-kinase enzyme activity
Examples: Growth Factors like PDGFs ( a family of factors which modulate the cell cycle)

23. Tyrosine-kinase in action
Ligand binding causes aggregation of 2 receptor units, forming receptor dimers
Aggregation activates the tyrosine-kinase activity in cytoplasm
These catalyze transfer of phosphate groups from ATP to tyrosine (an amino acid) in a protein. If this protein is part of the cytoplasmic T-K receptor, it’s called autophosphorylation

24. More T-K Receptor Action
4. The phosphorylated domain of the receptor reacts w/other proteins, resulting in the activation of another, RELAY protein or proteins. This can jump start MANY transduction systems simultaneously
5. One of the relay proteins may be PROTEIN PHOSPHATASE, which hydrolyzes a Phosphate off of proteins, possibly the tyrosines in the T-K receptors, thus inactivating them. Negative feedback? Yup.

25. Tyrosine-Kinase Reception

26. ION-Channel Receptors
Some signals bind to ligand-gated ion channels.
These are protein pores which open/close due to ligand binding, allowing/blocking the flow of specific ions (Na+, Ca2+)
ie.: Neurotransmitters
These can be on the plasma membrane OR in the cytoplasm or in the nucleus. The latter are called INTRACELLULAR RECEPTORS, and must be able to pass through the plasma membrane. ie: Steroids, Thyroid hormones, N.O.

27. The Structure of an Ion-gated channel

28. Signal Transduction Pathways
Pathways relay signals from receptorsCell responses: The ligand signal is not passed directly, but the signal INFORMATION is. At every step the signal is converted or transduced

29. Protein Phosphorylation as signal transduction
Caused by protein kinases
Very common
Commonly found in cytoplasm
Don’t act upon themselves (like T-K), but on other proteins, and attach phosphates to serine or threonine residues
Some activate, some deactivate target proteins
Protein Phosphatases reverse these

30. A Phosphorylation Cascade

31. Small Molecules/Ions are Important, too.
SECOND MESSENGERS: signal transduction components which are not proteins, but are small water soluble molecules or ions.
Two second messenger systems:
Cyclic AMP (cAMP) and
CA2+-Inositol Triphosphate (IP3) System

32. CYCLIC AMP Ligand binds to receptor(1st message)
Receptor conformation changes…G-Protein complex is activated
Active G-Protein activates adenyl cyclase (on cytoplasmic side of mem.)
Adenyl cyclase converts ATP to cAMP
cAMP binds to/activates protein kinase A
Protein kinase A phosphorylates various other proteins, leading to a cell response

33. CYCLIC AMP

34. cAMP as 2nd Messenger

35. Ca2+-IP3
Many cells induce a specific response by increasing their cytoplasm’s Ca+ concentration. Ca2+ can be increased by:
Ligand binding to Ca2+-gated ion channel
Activation of IP3 signaling pathway

36. IP. well IP2! Oh Yeah? Well IP3!!!!
ACTIVATION:
LigandConformational Chg. In receptor
Receptoractivates enzyme phospholipaseThese hydrolyze membrane phospholipidsgive rise to 2nd messengers: IP3 and diacylglycerol
DiacylglycerolProtein kinase
IP3 binds to Ca2+-gated channels on ER, where CA2+ is stored
CA2+signal transduction by affecting target proteins directly OR indirectly by binding indirectly to CALMODULINmodulates Protein kinases and phosphatases

37. Maintenance of Ca2+ in Animal cells

38. Ca2+ and IP3 in signaling pathways

39. Cellular Response Can involve regulation of cytoplasmic activities OR transcription in nucleus
IN CYTOPLASM:
Can affect function/activity of proteins which can:
Rearrange cytoskeleton
Open/close ion channels
Serve at key points in matabolic pathways
IN NUCLEUS:
Signaling system affects synthesis of new proteins/enzymes by modulating gene expression
Can regulate transcription(DNAmRNA) factors
Dysfunction in these can lead to cancer,etc

40. Cytoplasmic response

41. Nuclear Response

42. Amplification/Specification of Cell Response
AMPLIFICATION: Production of 2nd messengers (cAMP) intrinsically amplify signal. When this is linked to a phosphorylation cascade, the result is almost exponential
SIGNAL SPECIFICITY: Only target cells have the appropriate machinery to respond to a given signal (ligand).
Different cells can have different signal transduction pathways inside, so 1 signal molecule can affect different cells differently

43. Specificity of Cell Signaling