Signaling: Call Tracing Flashcards
Lecture 22
What is signal transduction?
ability of a cell to translate a receptor-ligand interaction to changes in its behavior or gene expression
What happens if there is an absence of a signal?
Can indicate time of cell death
What are the 6 classes of cell signals?
- Peptide hormones
- Steroid hormones
- Growth factors
- Cytokines
- Eicosanoids
- Neurotransmitters
What is the difference between growth factors and cytokines?
Growth factors signal when it is time for a cell to grow. Cytokines work similarly, but signal when it is time for a cell to proliferate.
What do cytokines do?
signal when it’s time for a cell to proliferate (divide, multiply, and populate)
What are eicosanoids?
cell signals; polyunsaturated fatty acids (20 carbons in length)
What do neurotransmitters do?
move signals through a chemical synapse, from one neuron to another
What are the four broad signaling classes?
- Paracrine
- Autocrine
- Endocrine
- Juxtacrine
What is paracrine signaling?
A cell releases a molecule into the external environment via exocytosis; a close, adjacent cell receives the signal on its surface; ex. neurotransmitters
What is juxtacrine signaling?
signaling where cells are in physical contact with each other at the plasma membrane; one cell presents a signaling molecule on its surface and the other cell binds directly with receptors for the signaling molecule
What is an examine of juxtacrine signaling?
immune cell recognition
What is an example of paracrine signaling?
neurotransmitters
What is autocrine signaling?
a single cell signals to itself; exocytoses a molecule that binds to receptors on the surface of the same cell
What is endocrine signaling?
hormones are dropped into the bloodstream, travel great distances from the source of the signal
What are the 2 main mechanisms for how signals get into cells? Which is more common? When is the less commonly used one used?
- Cell-surface receptors on the plasma membrane (common)
- Intracellular receptor (used when the signaling molecule is hydrophilic)
Why is the intracellular receptor route used when the signaling molecule is hydrophilic?
Because hydrophilic molecules don’t cross the plasma membrane (easily)
Why can hormones bind intracellular receptors to regulate transcription?
Because they are hydrophobic and able to pass through the plasma membrane
Describe the mechanism(s) for the flow of information during signal transduction utilizing cell surface receptors.
- A ligand/primary messenger binds to a receptor.
- Step 1 causes a conformational change in the structure of the receptor, triggering downstream events, producing secondary messengers.
3a. Signals interact with molecules in the cytoplasm that provoke an immediate cellular response.
3b. Signals enter the nucleus and change gene expression (activate or inactivate transcription).
How does intracellular signaling work?
Receptor is soluble and intracellular. The signaling molecule-intracellular receptor complex enters the nucleus and binds to a specific region of DNA to affect the transcription of a gene.
What are the two possible outcomes for the flow of information using cell surface receptors?
- Immediate cellular response in the cytosol
- Changes in gene expression in the nucleus by influencing transcription
What are the 3 different ways signals can be integrated?
- One receptor activates multiple pathways
- Different receptors activate the same pathway
- Different receptors activate different pathways; one pathway affects the other
Is altering gene expression or protein function with signaling faster?
Altering protein function is much faster.
What are the 3 classes of receptors on the cell surface that facilitate signal transduction?
- ion-channel linked receptor (ligand-gated channels)
- G-protein linked receptor
- enzyme-linked receptor
How do ligand-gated channels work?
Channels are activated when a ligand binds to the channel proteins (ex. neurotransmitters)
How many different G-protein linked receptors does the human genome code for?
2000
What’s the difference between G-protein linked receptors and other GTPase families?
G-protein linked receptors are heterotrimeric GTPases. They have 3 subunits that differ from one another. In contrast, the other G proteins are monomeric.
How are heterotrimeric G proteins activated?
activated when the heterotrimeric G-protein binds a G-protein coupled/linked receptor; the alpha subunit releases GDP and acquires GTP, separating from the beta-gamma complex
Describe the structure of G-protein linked receptors.
Large polypeptides
7 transmembrane alpha-helices
N terminus is exposed to extracellular fluid, C-terminus is in the cytosol
Extracellular portion has unique messenger-binding site
What does it mean when GDP is bound to the heterotrimeric G protein?
All 3 subunits are held together and the G protein is inactive.
Where does the nucleotide bind in the heterotrimeric G protein?
the alpha subunit
What causes the heterotrimeric G protein to bind to the receptor?
A signal molecule arrives at the receptor, causing the G protein to bind at a different site.
What happens to the heterotrimeric G protein after the signal molecule binds to the receptor?
GDP will come off the alpha subunit and will be replaced by GTP. The hterotrimeric G protein dissociates from the receptor and the beta-gamma complex of the two subunits separate from the activated GTP-bound alpha receptor
What happens when heterotrimeric GTPases hydrolyze GTP?
The three subunits come together and the cycle restarts.
How are secondary messengers created with G-linked protein receptors?
Activated alpha subunit binds and activates specific enzymes to produce specific second messengers.
What are 3 types of secondary messengers?
- cyclic mononucleotides (cAMP, cGMP)
- phosphoinositides (IP3)
- diacylglycerol
What protein catalyzes cAMP formation?
adenylyl cyclase
What does adenylyl cyclase do?
removes two phosphates, catalyzing cAMP formation from Atp
What does phospholipase C do?
cleaves PIP2 to yield IP3 and diacylglycerol (DAG)
When does adenylyl cyclase work?
when the alpha subunit of the heterotrimeric G-protein is GTP bound
When does phoshpodiesterase function in a cell?
when cells want to reduce the amount of signaling they receive
What does phosphodiesterase do?
hydrolyzes cAMP to AMP
Which subunit of the heterotrimeric G protein activates phospholipase C?
alpha subunit
What happens to diacylglycerol after it is produced?
The second messenger remains associated with the plasma membrane due to its two acyl chains. It can activate the protein kinase C.
What happens to the IP3 after it is produced?
The second messenger is released into the cytosol.