Cell Communication and Homeostasis

1. Cell Communication and Homeostasis

2. Dynamic Homeostasis

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. high low Generalized Negative Feedback Model hormone 1 lowersbody condition gland specific body condition raisesbody condition gland hormone 2

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

8. pancreas high liver low pancreas liver Endocrine System Control Feedback Regulation of Blood Sugar islets of Langerhans beta islet cells insulin body cells takeup sugar from blood liver storesglycogen reducesappetite blood sugar level (90mg/100ml) liver releasesglucose triggershunger islets of Langerhansalpha 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 high hormone 1 raisesbody condition gland specific body condition Or…

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

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. 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 system Amplification! 1 signal Activated adenylyl cyclase receptor protein Not yet activated 2 amplification 4 amplification 3 cAMP 5 amplification GTP G protein protein kinase 6 amplification enzyme Cascade multiplier! 7 amplification FAST response! product

27. http://bcs.whfreeman.com/thelifewire/content/chp15/15020.htmlhttp://bcs.whfreeman.com/thelifewire/content/chp15/15020.html 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 B A A B A C A B

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. Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene mRNA NUCLEUS 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”)

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