1. Cell Signaling
(Ch 13, kinda, ch 20, kinda)

2. Signal Transmission & Gene Expression
AKA – Cell Signaling Basics
(we will revisit this topic during body systems)
*Not really in textbook

3. Signal Transduction Pathway
“Signal” = chemical message that moves throughout body
2 types of signal transmissions
Intercellular – move from cell to cell to cell
Ex: Hormones of endocrine system, neurotransmitters of nervous system
Intracellular – move within cell itself
Ex: Apoptotic pathway (mitochondrial mediated)

4. Chemical messages (“signals”) can affect cell in two ways:
1. Immediate effect on cell function (change what cell is doing)
2. Lead to gene expression via DNA transcription and protein translation

5. Generic Pathway
Reception – Chemical message (ligand) docks at receptor on cell membrane and changes its shape
Transduction – switching message from chemical signal received on cell outside to chemical messages on interior of cell
Response –
Signal transduction cascade occurs until end result is reached

7. 2:15 signal transduction http://www. youtube. com/watch
2:15 signal transduction o :55 Cell communication

8. 1. Immediate Effect
A message (chemical signal) is transduced (and usually amplified) into actions within cell
Usually initiates a phosphorylation cascade which passes an energy-rich phosphate from one protein to another to another until desired action is carried out

9. Ex: Epinephrine Signaling
Epinephrine (ligand) is released by adrenal gland during “fight or flight” response
Ligand is a chemical that can't get through cell membrane thus binds receptor on outside
Epinephrine travels through body and binds to receptors on the outside of liver cells (high storage of glycogen)
Epinephrine receptor is a G-protein coupled receptor

11. G-protein is embedded within cell membrane; has three subunits inside the cell
Ligand binding changes the conformation of the GPCR and causes it to release alpha subunit
Alpha subunit moves to another protein called adenylyl cyclase
Binding causes conformational change which activates protein (enzyme)
Enzyme converts ATP → cAMP

13. 2 catalytic (speed up rxn rate)
cAMP – (secondary messenger) targets a protein kinase that has 4 subunits
2 catalytic (speed up rxn rate)
2 regulatory (regulate catalytic subunits)
If reg. subunits are attached to cat. → no action
cAMP binds to regulatory subunits  allosteric change in protein  catalytic subunits are released
Catalytic subunits get phosphorylated (activated)
Active catalytic subunits act on enzymes w/in cell
In this example, they activate phosphorylase, which breaks apart glycogen to release glucose

14. Why bother with all these steps?
Amplification

15. 2. Change Gene Expression
Pathway is the same UNTIL the catalytic subunits are activated
There are no proteins for these to act on, so instead they activate CREB (a transcription factor)
CREB binds to DNA upstream of gene to be expressed, bends DNA to facilitate transcription of mRNA, mRNA is translated into a protein called phosphatase which is able to break down glycogen

18. Generic Pathway
Reception – Chemical message (ligand) docks at receptor on cell membrane and changes its shape
Transduction – switching message from chemical signal received on cell outside to chemical messages on interior of cell
Response –
Signal transduction cascade occurs until end result is reached
Why?
Regulation and amplification!

19. 1. Immediate Effect
A message (chemical signal) is transduced (and usually amplified) into actions within cell
Usually initiates a phosphorylation cascade which passes an energy-rich phosphate from one protein to another to another until desired action is carried out

20. 2. Change Gene Expression
Pathway is the same UNTIL the catalytic subunits are activated
There are no proteins for these to act on, so instead they activate CREB (a transcription factor)
CREB binds to DNA upstream of gene to be expressed, bends DNA to facilitate transcription of mRNA, mRNA is translated into a protein called phosphatase which is able to break down glycogen

21. Changes to Pathways
“Correct” signal transduction pathways are under strong selective pressure
Changes that result in ineffective pathways are generally bad.
2 examples:
Diabetes
Botulism toxin
Botulism: rare and sometimes fatal paralytic illness
Botulinum toxin is one of the most powerful known toxins: about one microgram is lethal to humans.
It acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetyl choline's release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system.
This causes paralysis. Advanced botulism can cause respiratory failure by paralysing the muscles of the chest; this can progress to respiratory arrest.
illness is caused by the botulinium toxin produced by the bacterium C. botulinum in anaerobic conditions, and not by the bacterium itself

22. Ex: Diabetes Type I
Mutation results in autoimmune destruction of pancreatic beta cells (insulin producing cells)
Inability to produce insulin affects ability of glucose to enter cells

23. Ex: Botulinum Toxin (BTX)
Caused by bacterium Clostridium botulinum
Toxin inhibits acetylcholine nt (signal) from being released thus inhibiting muscle contraction
Leads to paralysis
Botulinum toxin is one of the most powerful known toxins: about one microgram is lethal to humans.
It acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetyl choline's release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system.
This causes paralysis. Advanced botulism can cause respiratory failure by paralysing the muscles of the chest; this can progress to respiratory arrest.
illness is caused by the botulinium toxin produced by the bacterium C. botulinum in anaerobic conditions, and not by the bacterium itself

25. Taste these samples in the following order: Salt
Equal® or Splenda (Aspartame)
Sugar
M&Ms®
Sour
2. Rate each substance for the perception of sweet, sour, bitter, and salt on a scale from 0 to 10 in the table below. A rating of “0” represents no perceived taste whereas a rating of “10” represents a very intense taste.
3. Optional: Rinse your mouth with water between each substance in order to avoid aftertaste mixtures.
4. Swish one ounce of Gymnema tea in your mouth for 30 seconds. Try to coat all areas of the mouth with the tea. Spit the tea into the sink when finished, then rinse your mouth briefly with water.
5. Beginning with salt, (and following the list above) re-taste each of the substances. Rate and record your perceptions of salty, sweet, bitter and sour for each substance on the following page.
Taste Lab

26. Taste Lab
what observations can you make about the effect of Gymnema sylvestre on the sense of taste? Which type(s) of taste does the tea alter?
How was your taste effected? (did is alter, eliminate, or enhance any tastes?)
What might be the possible mechanism for the effect of Gymnema on the perception of taste?