Cell Communication and Homeostasis  1

Dynamic Homeostasis  2

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?

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

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?

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

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

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

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?

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

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

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

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

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

Cell Signaling Signals can be stimulatory… or inhibitory.

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

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!)

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

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

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

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…

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

(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!

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

Benefits of a 2° messenger system 1 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

Step 3 - Response End results could be http://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!

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

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

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?

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

Phosphorylation Cascade

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