Lecture 11 - Second Messengers I Flashcards
What is the structure of CaMKII complexes?
CaMKII complexes are composed of two rosettes of 6 CaMKII subunits each stacked ontop of eachother.
What can neurotrophin receptor signaling lead to?
Cell Survival or Neurite Outgrowth and Neuronal Differentiation
What is protein phosphorylation equilibrium regulated by?
Kinases and Phosphatases
What acts as a GEF in monomeric G-protein systems?
The receptor itself acts as a GEF to replace GDP with GTP.
Which two second messengers come from phospholipase C?
Diacylglycerol and IP3
True or False?:
Muscarinic AChR in the heart cause hyperpolarization that is mediated by the direct effect of G protein on K+ channels.
True
Where is CaMKIV found?
In The Nucleus
What are the specific steps in the effector pathway leading to increased protein phosphorylation?
Norepinephrine → β-Adrenergic Receptor → Gs → + Adenylyl Cyclase → + cAMP → + Protein Kinase A → Increased Protein Phosphorylation
True or False?:
Pathways initiated at metabotropic receptors are isolated in the cytosol from those initiated at RTKs.
False
There is significant “cross-talk” (interaction) between pathways initiated at metabotropic receptors and pathways initated at RTKs.
What are the three types of signaling molecules?
Cell-Impermeant, Cell-Permeant, and Cell-Associated Molecules
An increase in which later effector results in an increase in protein phosphorylation?
Protein Kinase A
What are the specific steps in the effector pathway leading to decreased protein phosphorylation?
Dopamine → Dopamine D2 Receptor → Gi → - Adenylyl Cyclase → - cAMP → - Protein Kinase A → Decreased Protein Phosphorylation
True or False?:
Cyclic nucleotide-gated channels are ligand-gated by a cytosolic second messenger.
True
What are the steps in the effector pathways associated with G-protein-coupled receptors?
Neuotransmitter → Receptor → G-Protein → Effector Protein → Second Messenger → Later Effectors → Target Action
What target action is caused by the later effectors protein kinase C and Ca2+ release?
Increased Protein Phosphorylation and Activate Calcium-Binding Proteins
True or False?:
The trimeric G-protein is docked at a receptor until it is activated by a signal molecule.
False
The trimeric G-protein docks at a receptor when it is activated by a signal molecule.
True or False?:
Nitric oxide triggers adenylyl cyclase → cAMP → PKA signaling.
Nitric oxide triggers guanylyl cyclase → cGMP → PKG signaling.
What are the two types of G-proteins?
(Hetero)trimeric and Monomeric G-Proteins
True or False?:
RTKs dimerize, phosphorylate themselves, accumulate a signaling complex, and activate effortor proteins (like Ras).
True
What does IP3 do?
IP3 binds to IP3 receptors on the ER that cause it to release Ca2+ into the cytosol.
True or False?:
The PI cycle can be inhibited by magnesium.
False
The PI cycle can be inhibited by lithium.
What is an example of autoinhibition of neurotransmitter release?
G-Protein Inhibition of Ca2+ Channels
Which subunit binds GDP in the trimeric G-protein system?
α
What are the 5 steps of indirect synaptic transmission, starting with singalling cell and ending with a response?
Signaling Cell → Signal → Receptor → Target Molecule → Response
What is the benefit of an indirect signaling cascade?
An indirect signaling cascade through G-protein-coupled receptors results in an enormous amount of amplification.
What happens to the α, β, and γ subunits of the trimeric G-protein system between when GTP is bound and they return to the receptor?
The α subunit (bound to GTP) separates from the β and γ subunits when GTP is bound. The α subunit will bind to an effector protein, be dephosphorylated (by GAP), rebind with the β and γ subunits, and finally return to the receptor.
What does CREB phosphorylation lead to?
CREB phosphorylation leads to changes in gene expression.
What are the 3 types of the G protein α subunit (excluding G(olf))? What do they each do?
Gs - activates adenylyl cyclase, increasing cAMP production
Gi/o (Gi) - inhibits adenylyl cyclase, decreasing cAMP production
Gq - activates phospholipase C (PLC), causing the production of IP3 and diacyl glycerol (DAG)
Which G-protein α subunit is found on GABAB receptors?
Gi
What is the name of synaptic transmission using metabotropic receptors?
Indirect Synaptic Transmission
True or False?:
CREB is an important neuronal controller of polypeptide phosphorylation.
False
CREB is an important neuronal controller of gene expression.
Which type of cellular receptor are mGluR receptors, GABAB receptors, and most 5HT, NE, and DA receptors?
G-Protein-Coupled Receptors
True or False?:
Individual CaMKIIs phosphorylate their own phosphorylation site.
False
Individual CaMKIIs can’t phosphorylate their own phosphorylation site. Instead, they phosphorylate their neighbours.
True or False?:
PIP2 is split into IP3 and diacylglycerol.
True
Which RTK (receptor tyrosine kinase) is BDNF associated with?
TrkB
What are the two main functions of the G-protein βγ subunit?
- Increase activation of K+ channels (postsynaptically)
- Decrease activation of voltage gated Ca2+ channels (presynaptically)
How many transmembrane domains exist in G-protein-coupled receptors?
7
What activates PKC?
Diacylglycerol and Ca2+
What unbinds in PKC activation to allow for phosphorylation?
The catalytic domain unbinds from the regulatory domain when activated to allow for phosphorylation.
What facilitates the exchange of GDP for GTP?
Guanylyl Exchange Factors (GEF)
True or False?:
One G-protein-coupled receptor will interact with just one G-protein.
False
One G-protein-coupled receptor will interact with many G-proteins.
True or False?:
PKC can only affect substrates that are membrane-associated.
False
PKC can affect substrates that are not membrane-associated because the catalytic domain is “tethered” to and projects away from the regulatory domain, which is membrane-associated.
How does an inactive PKA become activated? What happens when it is activated?
An inactive PKA becomes activated when bound to cAMP. When activated, its conformation changes and the catalytic domains are released so that they can phosphorylate substrates.
Which type of cellular receptor is involved with indirect synaptic transmission?
G-Protein-Couple Receptors
True or False?:
Neurotransmitters primarily signal through trimeric G-proteins directly couple to the transmitter receptors.
True
True or False?:
PKA activates MAP kinase.
False
Ras activates MAP kinase (through ERKs).
True or False?:
Phosphorylation of a G-protein-coupled receptor by G-protein-couple receptor kinase (GRK) and binding of arrestin promote interaction with G proteins.
False
Phosphorylation of a G-protein-coupled receptor by G-protein-couple receptor kinase (GRK) and binding of arrestin prevent interaction with G proteins.
What are the amplifying steps in the effector pathways associated with G-protein-coupled receptors?
Receptor → G-Protein
Effector Protein → Second Messengers
Later Effectors → Target Action
How does an inactive CaMKII become activated? What happens when it is activated?
Inactive CaMKII is activated by calmodulin (CaM) bound to 4 Ca2+ ions. When activated, the regulatory domain separates from the catalytic domain so that it can phosphorylate substrate.
What are the steps of the PI cycle?
True or False?:
Ionotropic receptors are usually found at the center of the synapse while metabotropic receptors are generally found in the perisynaptic regions.
True
What happens when CaMKII phosphorylates itself?
When autophosphorylated, a CaMKII complex will stay in the open state even after Ca2+/CaM unbinds from the subunits.
What deactivates a G protein by dephosphorylating GTP?
GTP-ase Activating Protein (GAP)
