Secondary Messengers Flashcards
Secondary messengers mediate ___ signalling
intracellular
List 3 types of indirect transmission of signals
1) endocrine signalling
2) paracrine signalling
3) synaptic signalling
List 3 types of signalling molecules
1) cell impermeant molecules - require a receptor
2) cell permeant molecules - molecule diffuses right across membrane
3) cell surface signalling molecules - signaling occurs through direct binding of 2 cells close together
Is GPCR signalling slow or fast? Why?
Slow due to the time it takes to generate a signal cascade
Is ionotropic signalling considered fast or slow? Why?
Fast bc the ion channel opens, immediately allowing ions to flow through which allows the cell to quickly summate it and turn the signal into “make AP” or “don;t make AP”
Where in the synapse are metabotropic receptors located?
perisynaptic/peripheral area
T or F: activating only a few metabotropic receptors will yield a large effect
T
T or F: activating only a few ionotropic receptors will yield a small effect
T
Where is the NT binding site located on metabotropic receptors?
Middle of the channel
Do metabotropic receptors have large extracellular domains?
No
What do GAP proteins do?
Controls speed of GTP hydrolysis (GTP is bound to monomeric G protein)
Which enzyme is responsible for replacing GDP on monomeric G protein with GTP?
GEF
Name a common monomeric G protein
Ras
In a heterotrimeric G protein, which subunit acts as the GTPase?
alpha
Which subunit in a heterotrimeric G protein binds GTP?
alpha
What acts the GEF in a heterotrimeric G protein?
GPCR - activated GPCR allows alpha-GDP to be replaced with GTP
T or F: Only the alpha subunit of a G protein can activate downstream effectors
F - the beta/gamma subunit can as well
Which subunit of a heterotrimeric G protein is membrane bound?
Gamma
In basal state (ie not bound to a NT), is the GPCR associated with a G protein?
No
What does the Gi subunit do?
Inactivates adenylyl cyclase, leading to decreased cAMP production
What does Gq do?
Activates PLC, which generates IP3 + DAG
What kind of enzymes cleave IP3 to stop it from signalling? What is it cleaved into?
Phosphatases; inositol
Which molecule is DAG and IP3 generated from?
PIP2
Is DAG transmembrane or soluble?
transmembrane
What does DAG activate?
PKC
Which cycle do IP3 and DAG undergo to regenerate PIP2?
Phosphoinositol cycle
Which ion can be used to block the phosphoinositol cycle?
lithium
Which alpha subunit can be used to turn on ECB production?
Gq
In PKA, what does the regulatory domain act as?
pseudosubtrate to prevent catalytic kinase domain from being active all the time
Describe how GPCR signalling affects PKA activity
- alpha subunit (Gs) activates AC
- AC generates more cAMP
- cAMP binds to regulatory domain on PKA, causing conformational change that releases the catalytic domain
Which calcium binding protein activates CaMKII?
calmodulin
PKC is activated by ___ and coactivated by ___
DAG, Calcium
Name 4 categories of cellular receptors
- channel linked receptors/ionotropic
- enzyme linked receptors (ex. RTKs)
- intracellular receptors
- GPCRs/metabotropic
T or F: Ca is an intracellular secondary messenger
T
Name 2 sources of Ca:
- extracellular space
2. ER
T or F: Normally, intracellular concentrations of Ca are quite how
F - they are normally LOW
List 5 intracellular targets of Ca
Synaptotagmin kinases phosphatases calmodulin ion channels
List 3 Ca removal mechanisms
1) Ca exchangers and Ca pumps on plasma membrane
2) Ca pumps on ER membrane
3) mitochondria acts as a temporary Ca sink
List a ligand-gated channel that will allow Ca to enter the cell
NMDA, an ionotropic glutamate receptor
What activates the ryanodine channel on ER?
Calcium - generates a positive feedback loop for Ca release
How will an axon terminal with many mitochondria affect the length of time that the NT signals for?
The mt will sequester the Ca which is needed for NT release, therefore the synapse will not be able to signal for very long
How will an axon terminal with few mt affect signalling?
Ca will rise quickly because there are less mt to sequester it, therefore more signalling will occur since more vesicle fusion will occur
If you want more release of dense core vesicles, would your axon terminal require more or less mitcohondria?
Less - allows Ca levels to rise more quickly
What is the main purpose of CaMKII autophosphorylation?
Maintenance of Ca signal even after Ca is gone
T or F: many interneurons contain buffering CBP
T
Do buffering CBP cause downstream signalling?
No
Which proteins may be used to label interneurons?
Buffering CBP
How to Ca-binding dyes work?
They change their fluorescence when they bind to Ca
High Ca levels will result in increased phosphorylation or dephosphorylation?
High Ca –> activate kinases –> high phosphorylation
Low Ca levels will result in increased phosphorylation or dephosphorylation?
Low Ca –> activate phosphatases –> high dephosphorylation
