1. Warm-Up Why do you communicate? How do you communicate?
How do you think cells communicate?
Do you think bacteria can communicate? Explain.

2. Warm-Up
Compare the structure & function of these receptor proteins: GPCR, tyrosine kinase and ligand-gated ion channels.
What is a second messenger? What are some examples of these molecules?
What are the possible responses to signal transduction in a cell?

3. POGIL: Cell Communication
Table 1
Table 2
Table 3
Table 6
Station 7
Station 8
Group 9
Yafeit
Misah
Harley
Will
Pearson
Julia
Emmie
Marco
Hoyt
Benjamin
Mina
Hannah
George
Natalie
Everette
(Caitlin)
Duwe
Detlow
Elle
Langley
W. Shelley
Sidra
Biniyam
(Nayana)
Josue
Sarah DJ
Trinity

4. Cell Communication
CHAPTER 11

5. Do bacteria communicate?
Bonnie Bassler on How Bacteria “Talk”

6. Video Questions:
Why are scientists studying how bacteria (and not just human cells) communicate?
What is quorum sensing?
Describe how Vibrio fischeri use quorum sensing in squid.
According to Bonnie Bassler (Princeton University), what are scientists hoping to use as the next class of antibiotics?

7. Cell Signaling Animal cells communicate by:
Direct contact (gap junctions)
Secreting local regulators (growth factors, neurotransmitters)
Long distance (hormones)

8. Local/short distance; neurotransmitters move across a synapse
Long distance; hormones travel through bloodstream

9. 3 Stages of Cell Signaling:
Reception: Detection of a signal molecule (ligand) coming from outside the cell
Transduction: Convert signal to a form that can bring about a cellular response (often involves amplification)
Response: Cellular response to the signal molecule

10. Reception
Protein
Ligand

11. Transduction
Amplification

12. Response If in the nucleus, the response activates genes
If in cytoplasm, activates enzymes/proteins

13. 1. Reception
Binding between signal molecule (ligand) + receptor is highly specific.
Types of Receptors:
Plasma membrane receptor
Bind water-soluble ligands
Intracellular receptors (cytoplasm, nucleus)
hydrophobic or small ligands
Eg. testosterone or nitric oxide (NO)
Ligand binds to receptor protein  protein changes SHAPE  initiates transduction signal
Complementary shapes (just like enzymes and substrates!)
Allow for facilitated diffusion

14. Plasma Membrane Receptors Cell Surface Transmembrane Proteins
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinases
Ligand-Gated Ion Channels
Very widespread in animals/humans
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)

15. G-Protein-Coupled Receptor

16. G-Protein-Coupled Receptor
G protein is a molecular switch.
Inactive/off when GDP is bound
Active/on when GTP is bound
G proteins work together with an a receptor (GPCR)
G proteins work together with an enzyme (or other protein)

17. G-Protein-Coupled Receptor
Signaling molecule (ligand) binds to cytoplasm side of GPCR
Receptor is activated and changes shape.
Cytoplasm side of the receptor then binds inactive G protein, causing GTP to displace GDP
This activates the G protein

18. G-Protein-Coupled Receptor
Activated G protein leaves the receptor and moves down the membrane to an enzyme
Signaling molecule can bind/unbind many times
Activated enzyme changes shape and triggers next step in cell response.

19. G-Protein-Coupled Receptor
Changes in G protein and enzyme are temporary.
G protein also acts a GTPase enzyme (hyrdolyzes bound GTP to GDP)
Everything resets and G protein can be used again.

20. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Very widespread in animals/humans
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)
7 transmembrane segments in membrane
G protein + GTP activates enzyme  cell response

21. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Very widespread in animals/humans
Receptors that act as enzymes
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)
Transfers P group from ATP to the amino acid tyrosine
7 transmembrane segments in membrane
G protein + GTP activates enzyme  cell response

22. Receptor Tyrosine Kinase

23. Receptor Tyrosine Kinase
Signal molecules (ligands) binds to both monomers
Monomers come together and form a dimer (=dimerization)

24. Receptor Tyrosine Kinase
Each tyrosine kinase adds a phosphate from ATP to the tyrosines on the tails

25. Receptor Tyrosine Kinase
Relay proteins inside the cell bind to specific phosphorylated tyrosine, undergoes a shape change, and then triggers a transduction pathway leading to a cellular response.

26. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Very widespread in animals/humans
Receptors that act as enzymes
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)
Transfers P group from ATP to the amino acid tyrosine
7 transmembrane segments in membrane
Activate multiple cellular responses at once
G protein + GTP activates enzyme  cell response
Abnormal RTKs are associated with many cancers

27. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Very widespread in animals/humans
Receptors that act as enzymes
Region on receptor changes shape and acts like a “gate” when signal molecule binds
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)
Transfers P group from ATP to the amino acid tyrosine
Gates may open or close to regulate flow of specific ions
(Ca2+, Na+)
7 transmembrane segments in membrane
Activate multiple cellular responses at once
G protein + GTP activates enzyme  cell response
Abnormal RTKs are associated with many cancers

28. Ligand-Gated Ion Channel
Ligand binds to receptor (closed)  shape change  gate opens
The gate closes when the ligand dissociates
Ions flow into the cell through open gate; activates cell in some way

29. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Very widespread in animals/humans
Receptors that act as enzymes
Region on receptor changes shape and acts like a “gate” when signal molecule binds
Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)
Transfers P group from ATP to the amino acid tyrosine
Gates may open or close to regulate flow of specific ions
(Ca2+, Na+)
7 transmembrane segments in membrane
Activate multiple cellular responses at once
Important in nervous system
G protein + GTP activates enzyme  cell response
Abnormal RTKs are associated with many cancers
Some gated ion channels are controlled by electrical signals instead of ligands. These are voltage-gated ion channels

30. POGIL: Signal Transduction Pathways

31. The Fight or Flight Response

32. Bozeman Science: Signal Transmission and Gene Expression
Complete the review sheet while you watch

33. 2. Transduction
Cascades of molecular interactions relay signals from receptors to target molecules
Usually involve Protein kinases: enzymes that phosphorylate (transfer a phosphate group from ATP to a protein) and activate proteins at next level (turn signal on)
Protein phosphatases: enzymes that remove phosphate groups and inactivate protein kinases (can turn signal off)
Phosphorylation cascade: helps to enhance and amplify signal to allow a greater cellular response

35. Second Messengers
small, nonprotein molecules/ions that can relay signal inside cell
Eg. cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3)
Once activated, initiate a phosphorylation cascade

36. cAMP cAMP = cyclic adenosine monophosphate
GPCR  adenylyl cyclase (convert ATP  cAMP)  activate protein kinase A

37. 3. Response
Regulate protein synthesis by turning on/off genes in nucleus (gene expression)
Regulate activity of proteins (including enzymes) in cytoplasm

38. Bozeman Science Signal Transduction Pathways
Complete the review sheet while you watch

39. Signal Transduction Pathway Problems/Defects:
Examples:
Diabetes
Cholera
Autoimmune disease
Cancer
Neurotoxins, poisons, pesticides
Drugs (anesthetics, antihistamines, blood pressure meds)

40. Cholera
Toxin modifies G-protein involved in regulating salt & water secretion
G protein stuck in active form  intestinal cells secrete salts, water
Infected person develops profuse diarrhea and could die from loss of water and salts
Disease acquired by drinking contaminated water (w/human feces)
Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin

41. Viagra Used as treatment for erectile dysfunction
Inhibits hydrolysis of cGMP  GMP
Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis

42. Viagra inhibits cGMP breakdown

43. Apoptosis = cell suicide
Cell is dismantled and digested
Triggered by signals that activate cascade of “suicide” proteins (caspase)
Why?
Protect neighboring cells from damage
Animal development & maintenance
May be involved in some diseases (Parkinson’s, Alzheimer’s)

44. Apoptosis of a human white blood cell
Figure Apoptosis of human white blood cells
Left: Normal WBC
Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

45. Effect of apoptosis during paw development in the mouse
Figure Effect of apoptosis during paw development in the mouse

46. Bozeman Science Effects of Changes in Pathways
Complete the review sheet while you watch

47. Dropping Signals
Complete the online exploration and fill in the chart.
Read the article about Viagra and annotate.