Lecture 11 - Second Messengers I Flashcards

1
Q

What is the structure of CaMKII complexes?

A

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

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2
Q

What can neurotrophin receptor signaling lead to?

A

Cell Survival or Neurite Outgrowth and Neuronal Differentiation

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3
Q

What is protein phosphorylation equilibrium regulated by?

A

Kinases and Phosphatases

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4
Q

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

A

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

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5
Q

Which two second messengers come from phospholipase C?

A

Diacylglycerol and IP3

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6
Q

True or False?:

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

A

True

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7
Q

Where is CaMKIV found?

A

In The Nucleus

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8
Q

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

A

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

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9
Q

True or False?:

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

A

False

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

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10
Q

What are the three types of signaling molecules?

A

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

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11
Q

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

A

Protein Kinase A

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12
Q

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

A

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

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13
Q

True or False?:

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

A

True

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14
Q

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

A

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

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15
Q

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

A

Increased Protein Phosphorylation and Activate Calcium-Binding Proteins

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16
Q

True or False?:

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

A

False

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

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17
Q

True or False?:

Nitric oxide triggers adenylyl cyclase → cAMP → PKA signaling.

A

Nitric oxide triggers guanylyl cyclase → cGMP → PKG signaling.

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18
Q

What are the two types of G-proteins?

A

(Hetero)trimeric and Monomeric G-Proteins

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19
Q

True or False?:

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

A

True

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20
Q

What does IP3 do?

A

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

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21
Q

True or False?:

The PI cycle can be inhibited by magnesium.

A

False

The PI cycle can be inhibited by lithium.

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22
Q

What is an example of autoinhibition of neurotransmitter release?

A

G-Protein Inhibition of Ca2+ Channels

23
Q

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

A

α

24
Q

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

A

Signaling Cell → Signal → Receptor → Target Molecule → Response

25
Q

What is the benefit of an indirect signaling cascade?

A

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

26
Q

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?

A

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.

27
Q

What does CREB phosphorylation lead to?

A

CREB phosphorylation leads to changes in gene expression.

28
Q

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

A

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)

29
Q

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

A

Gi

30
Q

What is the name of synaptic transmission using metabotropic receptors?

A

Indirect Synaptic Transmission

31
Q

True or False?:

CREB is an important neuronal controller of polypeptide phosphorylation.

A

False

CREB is an important neuronal controller of gene expression.

32
Q

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

A

G-Protein-Coupled Receptors

33
Q

True or False?:

Individual CaMKIIs phosphorylate their own phosphorylation site.

A

False

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

34
Q

True or False?:

PIP2 is split into IP3 and diacylglycerol.

A

True

35
Q

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

A

TrkB

36
Q

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

A
  • Increase activation of K+ channels (postsynaptically)
  • Decrease activation of voltage gated Ca2+ channels (presynaptically)
37
Q

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

A

7

38
Q

What activates PKC?

A

Diacylglycerol and Ca2+

39
Q

What unbinds in PKC activation to allow for phosphorylation?

A

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

40
Q

What facilitates the exchange of GDP for GTP?

A

Guanylyl Exchange Factors (GEF)

41
Q

True or False?:

One G-protein-coupled receptor will interact with just one G-protein.

A

False

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

42
Q

True or False?:

PKC can only affect substrates that are membrane-associated.

A

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.

43
Q

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

A

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.

44
Q

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

A

G-Protein-Couple Receptors

45
Q

True or False?:

Neurotransmitters primarily signal through trimeric G-proteins directly couple to the transmitter receptors.

A

True

46
Q

True or False?:

PKA activates MAP kinase.

A

False

Ras activates MAP kinase (through ERKs).

47
Q

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.

A

False

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

48
Q

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

A

Receptor → G-Protein

Effector Protein → Second Messengers

Later Effectors → Target Action

49
Q

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

A

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.

50
Q

What are the steps of the PI cycle?

A
51
Q

True or False?:

Ionotropic receptors are usually found at the center of the synapse while metabotropic receptors are generally found in the perisynaptic regions.

A

True

52
Q

What happens when CaMKII phosphorylates itself?

A

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

53
Q

What deactivates a G protein by dephosphorylating GTP?

A

GTP-ase Activating Protein (GAP)