1. Cell Communication and Homeostasis 1

2. Dynamic Homeostasis  2

3. What is (dynamic) homeostasis?
Homeostasis = The property of a system that regulates its internal environment to maintain stable, (relatively) constant conditions
In living things, often termed “dynamic homeostasis” - what do you figure this indicates?

4. Feedback Control
Homeostasis is often maintained through the use of feedback systems (or loops).
A feedback system uses the consequences of the process (too much or too little produced) to regulate the rate at which the process occurs
Consists of a sensor, a control center, and an effector pathway

5. Positive vs Negative Feedback loops may be positive or negative
Negative feedback mechanism: Maintains homeostasis by returning a changing condition back to its stable target point
Discussion: although there are negative and positive operons, both types are a negative feedback mechanism - why?

6. Generalized Negative Feedback Model
hormone 1
gland
lowers body condition
high
specific body condition
low
raises body condition
gland
hormone 2

7. Controlling Body Temperature
Nervous System Control
Feedback
Controlling Body Temperature
nerve signals
hypothalamus
sweat
dilates surface blood vessels
high
body temperature
(37°C)
low
hypothalamus
constricts surface blood vessels
shiver
nerve signals

8. Regulation of Blood Sugar
Endocrine System Control
Feedback
Regulation of Blood Sugar
islets of Langerhans beta islet cells
insulin
body cells take up sugar from blood
liver stores glycogen
reduces appetite
pancreas
liver
high
blood sugar level
(90mg/100ml)
low
liver releases glucose
triggers hunger
pancreas
liver
islets of Langerhans alpha islet cells
glucagon

9. Positive vs Negative
Alterations in negative feedback mechanisms -> deleterious consequences
Discussion: People who are diabetic produce minimal insulin. What effect does this have on the blood sugar control feedback loop?

10. Positive vs Negative
Positive feedback mechanism: Does not maintain homeostasis; instead, amplifies responses and processes, moving the system further and further away from starting conditions.
Example: labor in childbirth

11. Generalized Positive Feedback Model
hormone 1
gland
raises body condition
high
specific body condition
Or… 11

12. Generalized Positive Feedback Model
hormone 1
gland
lowers body condition
low
specific body condition 12

13. Discussion
Describe a positive feedback loop in the case of asthma, taking into account variables such as:
airway swelling/narrowing
aiway irritation
blood oxygen levels
cortisol increasing heart & breathing rates
lung oxygen content
nervous system recognition of blood oxygen levels
oxygen available to brain
panic
release of stress hormones such as cortisol

14. Cell Signaling  15

15. Cell Signaling
Every feedback loop in an organism that we discussed, positive or negative, has one thing in common: cell signaling.
In a multicellular (and even unicellular!) organism, recognizing and responding to changes, internal or external, requires cell-to-cell communication
Cells do this by generating, transmitting, and receiving chemical signals

16. Cell Signaling
Signals can be
stimulatory…
or inhibitory.

17. Cell Signaling
Cell signaling (sometimes just called “signal transduction”) has three general stages:
Reception
Transduction
Response

18. Step 1 - Reception Reception
Signaling begins with the recognition of a chemical messenger by a receptor protein
Chemical messenger = a ligand
Different receptors “recognize” different ligands due to fit, in a one-to-one relationship (think enzymes!)

19. Step 1 - Reception Receptor proteins may be either:
embedded in the cell membrane
Examples: G protein receptors, ligand-gated ion channels

20. Step 1 - Reception or: in the cytoplasm or even nucleus
In these cases, a hydrophobic ligand diffuses into the cell
Examples: steroid hormones, nitric oxide

21. Step 1 - Reception
The ligand binding to the receptor changes the receptor’s conformation (shape), which initiates the next step, transduction

22. Step 2 - Transduction
Signal transduction is the process by which a signal is converted to a cellular response.
The activated receptor affects another molecule, which affects another, which affects another…

23. Step 2 - Transduction
When the receptor protein changes conformation, it may…
Serve as an enzyme
Open up a channel between cell interior and exterior (like ion channels in neurons!)
Release a polypeptide from itself into the cytoplasm
…which is the first in what will be a series of chemical reactions, largely involving proteins…
…but using at least one small, non-protein second messenger.
Common second messengers: ions (Ca2+), cAMP

24. (Remember cAMP?) Fun fact! Glucose high = cAMP low ring a bell?
That’s actually because of one such multistep process!
When glucose passes into the cell, one step in the process involves inhibiting adenylate cyclase, an enzyme which otherwise is busy producing the second messenger cAMP!

25. Step 2 - Transduction Signal transduction = efficiency!
Due to signal amplification: some steps in transduction activate multiples of the next step
So, a single ligand can trigger a large response

26. Benefits of a 2° messenger system1
signal
Activated adenylyl cyclase
receptor protein 2
Not yet
activated
amplification 4
amplification 3
cAMP
amplification 5
GTP
G protein
protein kinase 6
amplification
Amplification!
enzyme
Cascade multiplier! 7
amplification
FAST response!
product

27. Step 3 - Response End results could be
Step 3 - Response
End results could be
producing or destroying transcription factors (turns genes on/off)
activating enzymes
cytoskeleton rearrangement
many more!

28. Signal Transduction
Signal transduction diagrams can follow some slightly different conventions, but common ones are:
A stimulates B
A inhibits B
Translocation/Relocation
B to C is a larger (amplified) response than A to B A B A B A A B C

29. Signal Transduction A and B subunits join to make C
A separates into subunits B and C
Multistep pathway from A to B with some steps not shown A C B B A C A B

30. Discussion
Consider this very simple diagram of a signal cascade (bigger image on next slide), and answer:
What’s happening? What is the ligand? What is the second messenger (hint: not necessarily named)? Does EGF trigger or inhibit gene regulation?

32. Signal Transduction
That example displayed a common signal transduction method: a phosphorylation cascade
A series of protein kinases adding a phosphate group to the next protein in the sequence (remember kinase = “activator”)
Reception
Transduction
Response
mRNA
NUCLEUS
Gene P
Active
transcription
factor
Inactive
DNA
Phosphorylation
cascade
CYTOPLASM
Receptor
Growth factor

33. Phosphorylation Cascade

34. Cell Signaling Specificity
Which receptors and secondary messengers a cell possesses determines which signals it will respond to, and how
This is why a liver and a heart cell will do two different things when activated by the same hormone, like epinephrin