1. Cell Communication

2. 2 Major Mechanisms of Communication
Negative Feedback: Stopping a signal in response to a sufficient amount of the end product; “counter-acting”
Ex: Regulating Blood Sugar
Positive Feedback: Cell signal will continue as long as stimulus is available; “promoting”
Ex: Oxytocin (hormone that stimulates muscle contraction)

3. Cell Signaling Animal cells communicate by: Direct contact
Gap junctions
Antibodies
Local Signaling
Paracrine: vesicle-mediated
Growth Factors
Synaptic: channel-mediated
Neurotransmitters
Long distance (hormones)

5. 3 Stages of Cell Communication:
Reception: Ligand binds to receptor protein on cell’s surface, causing protein to change shape
Transduction: Convert signal to a form that can bring about a cellular response; usually multi-step
Response: Cellular response to the signal molecule; may cause cell to produce something or regulate a cellular processes

6. Reception

7. Transduction

8. Response

9. 1. Reception
Binding between signal molecule (ligand) + receptor is highly specific.
Types of Receptors:
Plasma membrane receptor proteins
water-soluble ligands
Intracellular receptor proteins (cytoplasm, nucleus)
hydrophobic or small ligands
Most often are steroids
Ligand binds to receptor protein  protein changes SHAPE  initiates transduction signal

10. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Ligand binds to GPCR, changing shape of GPCR
Shape change causes G protein subunit to be released
Released G protein subunit then docks with another protein (or enzyme), which will relay the signal further

11. G-Protein-Coupled Receptor

12. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Ligand binds and kinases dimerize
Activated kinases accept phosphate group from ATP (activates kinase)
Relay proteins take phosphate groups away to activate multiple cellular response

13. Receptor Tyrosine Kinase

14. Plasma Membrane Receptors
G-Protein Coupled Receptor (GPCR)
Tyrosine Kinase
Ligand-Gated Ion Channels
Ligand binds to protein receptor, allowing gate to open
Ions are able to pass through cell membrane
When ligand detaches, gate closes

15. Ligand-Gated Ion Channel

16. 2. Transduction: multi-step signal that relays chemical signal from receptor to response
Two methods of transduction:
Phosphorylation Cascade
Involves transfer of phosphate groups to/from ATP within protein pathway
Kinases: activate proteins (add phosphate)
Phosphatases: deactivate proteins (remove phosphates)
Second messengers
Use of non-protein molecules to relay signals; sometimes activate cascades

17. Results in phosphorylation (activation) of thousands of proteins
Energy is taken from original relay molecule to activate cascade, which then takes the “activation” signal to a specific protein (the target of the original signal), to elicit a cellular response

18. Second Messengers
small, nonprotein molecules/ions that can relay signal inside cell
Eg. cyclic AMP (cAMP), calcium ions (Ca2+)

19. cAMP cAMP = cyclic adenosine monophosphate
GPCR  activates/releases G proteintravels to adenylyl cyclase (convert ATP to cAMP)  activate protein kinase A

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

21. Let’s visualize this!
Epinephrine pathway:

22. Signal Transduction Pathway Problems/Defects:
Examples:
Diabetes
Autoimmune disease
Cancer
Drugs (anesthetics, antihistamines, blood pressure meds)

23. Viagra Used as treatment for erectile dysfunction
Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis

24. 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)

25. 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”)

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