Lecture 11 - Second Messengers I

Question 1

What is the structure of CaMKII complexes?

Answer 1

CaMKII complexes are composed of two rosettes of 6 CaMKII subunits each stacked ontop of eachother.

Question 2

What can neurotrophin receptor signaling lead to?

Answer 2

Cell Survival or Neurite Outgrowth and Neuronal Differentiation

Question 3

What is protein phosphorylation equilibrium regulated by?

Answer 3

Kinases and Phosphatases

Question 4

What acts as a GEF in monomeric G-protein systems?

Answer 4

The receptor itself acts as a GEF to replace GDP with GTP.

Question 5

Which two second messengers come from phospholipase C?

Answer 5

Diacylglycerol and IP₃

Question 6

True or False?:

Muscarinic AChR in the heart cause hyperpolarization that is mediated by the direct effect of G protein on K+ channels.

Answer 6

True

Question 7

Where is CaMKIV found?

Answer 7

In The Nucleus

Question 8

What are the specific steps in the effector pathway leading to increased protein phosphorylation?

Answer 8

Norepinephrine → β-Adrenergic Receptor → G_s → + Adenylyl Cyclase → + cAMP → + Protein Kinase A → Increased Protein Phosphorylation

Question 9

True or False?:

Pathways initiated at metabotropic receptors are isolated in the cytosol from those initiated at RTKs.

Answer 9

False

There is significant “cross-talk” (interaction) between pathways initiated at metabotropic receptors and pathways initated at RTKs.

Question 10

What are the three types of signaling molecules?

Answer 10

Cell-Impermeant, Cell-Permeant, and Cell-Associated Molecules

Question 11

An increase in which later effector results in an increase in protein phosphorylation?

Answer 11

Protein Kinase A

Question 12

What are the specific steps in the effector pathway leading to decreased protein phosphorylation?

Answer 12

Dopamine → Dopamine D2 Receptor → G_i → - Adenylyl Cyclase → - cAMP → - Protein Kinase A → Decreased Protein Phosphorylation

Question 13

True or False?:

Cyclic nucleotide-gated channels are ligand-gated by a cytosolic second messenger.

Answer 13

True

Question 14

What are the steps in the effector pathways associated with G-protein-coupled receptors?

Answer 14

Neuotransmitter → Receptor → G-Protein → Effector Protein → Second Messenger → Later Effectors → Target Action

Question 15

What target action is caused by the later effectors protein kinase C and Ca²⁺ release?

Answer 15

Increased Protein Phosphorylation and Activate Calcium-Binding Proteins

Question 16

True or False?:

The trimeric G-protein is docked at a receptor until it is activated by a signal molecule.

Answer 16

False

The trimeric G-protein docks at a receptor when it is activated by a signal molecule.

Question 17

True or False?:

Nitric oxide triggers adenylyl cyclase → cAMP → PKA signaling.

Answer 17

Nitric oxide triggers guanylyl cyclase → cGMP → PKG signaling.

Question 18

What are the two types of G-proteins?

Answer 18

(Hetero)trimeric and Monomeric G-Proteins

Question 19

True or False?:

RTKs dimerize, phosphorylate themselves, accumulate a signaling complex, and activate effortor proteins (like Ras).

Answer 19

True

Question 20

What does IP₃ do?

Answer 20

IP₃ binds to IP₃ receptors on the ER that cause it to release Ca²⁺ into the cytosol.

Question 21

True or False?:

The PI cycle can be inhibited by magnesium.

Answer 21

False

The PI cycle can be inhibited by lithium.

Question 22

What is an example of autoinhibition of neurotransmitter release?

Answer 22

G-Protein Inhibition of Ca²⁺ Channels

Question 23

Which subunit binds GDP in the trimeric G-protein system?

Answer 23

α

Question 24

What are the 5 steps of indirect synaptic transmission, starting with singalling cell and ending with a response?

Answer 24

Signaling Cell → Signal → Receptor → Target Molecule → Response

Question 25

What is the benefit of an indirect signaling cascade?

Answer 25

An indirect signaling cascade through G-protein-coupled receptors results in an enormous amount of amplification.

Question 26

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?

Answer 26

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.

Question 27

What does CREB phosphorylation lead to?

Answer 27

CREB phosphorylation leads to changes in gene expression.

Question 28

What are the 3 types of the G protein α subunit (excluding G(olf))? What do they each do?

Answer 28

G_s - activates adenylyl cyclase, increasing cAMP production G_i/o (G_i) - inhibits adenylyl cyclase, decreasing cAMP production G_q - activates phospholipase C (PLC), causing the production of IP₃ and diacyl glycerol (DAG)

Question 29

Which G-protein α subunit is found on GABAB receptors?

Answer 29

G_i

Question 30

What is the name of synaptic transmission using metabotropic receptors?

Answer 30

Indirect Synaptic Transmission

Question 31

# True or False?: CREB is an important neuronal controller of polypeptide phosphorylation.

Answer 31

False CREB is an important neuronal controller of gene expression.

Question 32

Which type of cellular receptor are mGluR receptors, GABAB receptors, and most 5HT, NE, and DA receptors?

Answer 32

G-Protein-Coupled Receptors

Question 33

# True or False?: Individual CaMKIIs phosphorylate their own phosphorylation site.

Answer 33

False Individual CaMKIIs can't phosphorylate their own phosphorylation site. Instead, they phosphorylate their neighbours.

Question 34

# True or False?: PIP₂ is split into IP₃ and diacylglycerol.

Answer 34

True

Question 35

Which RTK (receptor tyrosine kinase) is BDNF associated with?

Answer 35

TrkB

Question 36

What are the two main functions of the G-protein βγ subunit?

Answer 36

* Increase activation of K⁺ channels (postsynaptically) * Decrease activation of voltage gated Ca²⁺ channels (presynaptically)

Question 37

How many transmembrane domains exist in G-protein-coupled receptors?

Answer 37

7

Question 38

What activates PKC?

Answer 38

Diacylglycerol and Ca²⁺

Question 39

What unbinds in PKC activation to allow for phosphorylation?

Answer 39

The catalytic domain unbinds from the regulatory domain when activated to allow for phosphorylation.

Question 40

What facilitates the exchange of GDP for GTP?

Answer 40

Guanylyl Exchange Factors (GEF)

Question 41

# True or False?: One G-protein-coupled receptor will interact with just one G-protein.

Answer 41

False One G-protein-coupled receptor will interact with many G-proteins.

Question 42

# True or False?: PKC can only affect substrates that are membrane-associated.

Answer 42

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.

Question 43

How does an inactive PKA become activated? What happens when it is activated?

Answer 43

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.

Question 44

Which type of cellular receptor is involved with indirect synaptic transmission?

Answer 44

G-Protein-Couple Receptors

Question 45

# True or False?: Neurotransmitters primarily signal through trimeric G-proteins directly couple to the transmitter receptors.

Answer 45

True

Question 46

# True or False?: PKA activates MAP kinase.

Answer 46

False Ras activates MAP kinase (through ERKs).

Question 47

# 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.

Answer 47

False Phosphorylation of a G-protein-coupled receptor by G-protein-couple receptor kinase (GRK) and binding of arrestin prevent interaction with G proteins.

Question 48

What are the amplifying steps in the effector pathways associated with G-protein-coupled receptors?

Answer 48

Receptor → G-Protein Effector Protein → Second Messengers Later Effectors → Target Action

Question 49

How does an inactive CaMKII become activated? What happens when it is activated?

Answer 49

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.

Question 50

What are the steps of the PI cycle?

Answer 50

Question 51

# True or False?: Ionotropic receptors are usually found at the center of the synapse while metabotropic receptors are generally found in the perisynaptic regions.

Answer 51

True

Question 52

What happens when CaMKII phosphorylates itself?

Answer 52

When autophosphorylated, a CaMKII complex will stay in the open state even after Ca²⁺/CaM unbinds from the subunits.

Question 53

What deactivates a G protein by dephosphorylating GTP?

Answer 53

GTP-ase Activating Protein (GAP)