Week 10 Flashcards
Gene involved in generating oscillations in the body’s day/night cycle
Per
Wnt pathway basic characteristics
- Wnt from wingless in Drosophila and Int1 in mice
- Secreted signaling molecule
- Fatty acid covalently attached to their N-terminus, allowing them to bind to cell surfaces and create local gradients.
What does Wnt signaling regulate?
Proteolysis of Beta-catenin
What happens to the B-catenin molecule in the Wnt pathway?
- B-catenin is an important effector molecule in the signal pathway
- Gets phosphorylated, ubiquitinated, and targeted for the proteosome.
Role of degradation complex in Wnt pathway
- Keeps the proteins close and scaffolded to recruit kinases so necessary proteins (like B-catenin) can be degraded
- In the presence of Wnt signal, the degradation complex is destroyed, so B-catenin is then in turn not degraded.
What protein must be activated to recruit Dishevelled in the Wnt pathway?
The Frizzled receptor
How does Hedgehog collaborate with Wnt in development?
Different neuronal identities are dictated by the combination of Wnt and Hedgehog signaling experienced by each cell. How much of the two ligands (Wnt and Hedgehog) a neuron experiences will determine its fate.
Four things that explain the real-life signaling dynamic observed in cells that a linear signaling pathway cannot capture
- Response timing
- Sensitivity
- Dynamic range
- Persistence
Response timing
Speed of a response
Sensitivity
Likelihood of a response to stimulus
Dynamic range
Range of stimulus intensity that a signaling pathway is sensitive to
Persistence
How long a response persists after a transient stimulus
What does the speed of a response depend on?
The speed of a response depends on the turnover (half-life) of signaling molecules
Half-life relationship to decrease in synthesis rate
If stimulus triggers a decrease in synthesis rate of a signaling molecule, the drop in its relative concentration is quicker for molecules with short half-life
Half-life relationship to increase in synthesis rate
If stimulus triggers an increase in synthesis rate of a signaling molecule, the rise in its relative concentration is also quicker for molecules with short half-life
Relationship between sharpness of activation and number of effector molecules
Sharpness of activation increases with increasing number of effector molecules that must be simultaneously bound to the target protein
Because four molecules of Ca2+ are required to activate one molecule of calmodulin, what type of response is this?
This results in a binary response (if only one Ca2+ ion were required, it would be a linear relationship. 1:1 ratio results in linear relationship)
When are all or none responses important?
All or none responses are important when a cellular decision needs to be permanent. E.g. apoptosis, cell fate
When is negative feedback useful?
Negative feedback can help prevent accidental activation of a signaling pathway due to background ‘noise’.
When is positive feedback useful?
Positive feedback loop can be used to sustain a response, even after the original signal is extinguished. In other words, it can be used to ‘remember’ the stimulus
Role of CaM-kinase II
CaM-kinase II acts as a ‘memory’ molecule, remaining active even after calcium signal decay. Involved in learning and memory
What happens after calcium binds to calmodulin?
- Calmodulin binds to the linker region
- Kinase is in popped out state, meaning it’s active
- The kinase domain phosphorylates the linker region, keeping it in a popped out state
How are oscillations related to Gq mediated IP3 production?
- Gq mediated IP3 production releases calcium from ER in an oscillatory manner.
- Calcium activates IP3 and ryanodine receptors on ER membrane at lows levels, but inhibits them at high concentrations.
Effect on calcium with increasing stimulation of vasopressin
The frequency, not the amplitude of the calcium spikes increases with increasing stimulation from vasopressin
What type of feedback generates the circadian clock?
Delayed negative feedback
With increasing stimulation from vasopressin, why does the frequency but not amplitude of the calcium spikes increase?
- The negative feedback loops caps the amount of calcium allowed in the cytosol.
- At a certain concentration, calcium will start to inhibit its own release, which means amplitude is capped at that concentration.
How does a delayed negative feedback loop generate the circadian clock?
After transcription and translation, Per forms a heterodimer with Tim (which is also transcribed and translated). Then the heterodimer will reenter the nucleus to inhibit Per and Tim. This is an example of a negative feedback loop because Per inhibits its own expression. Oscillations in the levels of Per and Tim generate the body’s circadian clock.
Role of DBT kinase
DBT kinase targets Per for degradation.
Three major cytoskeleton filaments and main difference between them
- Actin filaments
- Microtubules
- Intermediate filaments
Actin filaments and microtubules are asymmetric, while intermediate filaments are symmetric