Molecular Signaling in Neurons Flashcards

1
Q

3 classes of cell signaling molecules

A

Cell impermeant molecules
Cell permeant molecules
Cell associated molecules

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2
Q

Most neurotransmitters are ___ ____ molecules.

A

Cell impermeant

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3
Q

In cell impermeant molecules, the signal (neurotransmitter) can be contained in a lipid ____.

A

Vesicle

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4
Q

Cell impermeant molecule receptors must be on the cell _____.

A

Surface

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5
Q

3 examples of cell permeant molecules (2 unconventional neurotransmitters, 1 hormone)

A

Endocannabinoids
NO
Estrogen

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6
Q

Can cell permeant molecules be contained in a vesicle? Why or why not?

A

No- are lipid soluble so can pass through vesicle

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7
Q

Cell permeant molecules can bind receptors on the cell ___ or ____ the cell.

A

Surface

Inside

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8
Q

Cell associated molecules include adhesion molecules such as ____ or _____.

A

Integrins

Ephrins

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9
Q

Cell associated molecules can signal (uni-/bi-directionally). Why?

A

Bi-directionally

Molecules in both cells could be considered receptor or ligand

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10
Q

4 types of cellular receptors

A

Channel-linked receptors
Enzyme-linked receptors
G-protein coupled receptors
Intracellular receptors

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11
Q

Channel-linked receptors include the _____-_____ ____ channels and are gated by _____, or secreted molecules.

A

Ligand gated ion

Ligands

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12
Q

With enzyme-linked receptors, binding on the _____ side induces _____ change that activates ____ on the ____ side.

A

Extracellular
Conformational
Enzyme
Intracellular

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13
Q

Enzyme-linked receptors bind what 2 types of cell signaling molecules? What is an example of each?

A

Cell-impermeant molecules (neurotrophin)

Cell-associated molecules (integrins)

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14
Q

With G protein-coupled receptors, binding on the _____ side induces _____ change that enables association with ____ _____ on the ____ side.

A

Extracellular
Conformational
G proteins
Intracellular

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15
Q

G protein-coupled receptors usually bind ___ ____ molecules, but can bind other types of ligands.

A

Cell impermeable

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16
Q

Intracellular receptors bind only _____ _____ molecules because they are located only on the intracellular side.

A

Cell permeant

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17
Q

What are the best known type of intracellular receptors?

A

Estrogen receptors

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18
Q

What 2 types of cellular receptors are considered to be “typical” neurotransmitter receptors, and which 2 are not?

A

“Typical”: channel-linked, G protein-coupled

Not “typical”: enzyme-linked, intracellular

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19
Q

3 types of signaling

A

Synaptic
Paracrine
Endocrine

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20
Q

In which type of signaling are the cells located the closest to each other?

A

Synaptic

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21
Q

In synaptic signaling, the ligand can be how many of the 3 types of cell signaling molecules?

A

All (cell permeant, impermeant, or associated)

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22
Q

Most neurotransmitter signaling falls under which of the 3 categories?

A

Synaptic

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23
Q

In paracrine signaling, are the cells located close, intermediate, or far away from each other? This is because the cells are ____ each other, but don’t share an ____ ____.

A

Intermediate
Near
Active zone

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24
Q

3 examples of molecules that use paracrine signaling (2 are neurotransmitter types)

A

Hormones
Endocannabinoids
Neuropeptides

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25
Q

Paracrine and endocrine signaling can use either cell ___ or ___ molecules, but not cell ____ molecules for signaling.

A

Permeant
Impermeant
Associated

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26
Q

In which type of signaling are the cells the farthest away from each other?

A

Endocrine

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27
Q

In endocrine signaling, the signal travels through the ____ ____. What type of molecules are used in this type of signaling?

A

Blood stream

Hormones

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28
Q

Second messengers are (intracellular/extracellular) signaling molecules that are released by the cell in response to (intracellular/extracellular) signaling molecules, the first messengers.

A

Intracellular

Extracellular

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29
Q

Second messengers include _____, ____, and ____.

A

Nucleotides (ATP, etc)
Ions (Ca+2, etc)
Phospholipids (PIP2, etc)

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30
Q

Binding of a second messenger induces a conformational change in the ____, which is downstream in the signaling pathway. This could cause (activation/inactivation/both) of this molecule.

A

Effector

Both

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31
Q

In phosphorylation, ____ is used as the source of phosphate.

A

ATP

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32
Q

What is the name of the enzyme that takes the phosphate group off of ATP? What type of bond does it use to attach the phosphate to its target?

A

Kinase

Covalent

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33
Q

Phosphorylation of a target induces ____ change that (activates/inhibits/both) the target.

A

Conformational

Both

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34
Q

What is the name of the enzyme that breaks the covalent phosphate bond and removes the phosphate from the target, inducing a conformational change in the target?

A

Phosphatase

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35
Q

Phosphate groups are normally added to which 3 amino acids of a target protein?

A

Serine, threonine, tyrosine

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36
Q

Signal amplification: ____ (number) ligand(s) binding to a receptor activates (one/many) downstream effectors.

A

One

Many

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37
Q

2 types of GTP binding proteins (think number of subunits)

A

Heterotrimeric G proteins

Monomeric G proteins

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38
Q

Are the heterotrimeric or monomeric G proteins used more in neurotransmitter signaling? Which one plays a greater role in cell cycle?

A

Heterotrimeric

Monomeric

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39
Q

In a heterotrimeric G protein, are the subunits encoded by the same or different genes?

A

Different

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40
Q

Inactive heterotrimeric G proteins bind to (GTP/GDP).

A

GDP

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41
Q

Both heterotrimeric and monomeric G proteins bind to ____ to become activated and have _____ activity that enables them to hydrolyze ____ to ____.

A

GTP
GTPase
GTP
GDP

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42
Q

Hydrolyzing GTP to GDP turns a G protein ___.

A

Off

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43
Q

When ligand binds to a G protein coupled receptor (GPCR), a ____ change in the receptor occurs that enables interaction with a ____ _____. That interaction enables a ______ change to occur in the _____ subunit of that protein, causing it to exchange ____ for ___, which activates it. The activated subunit interacts with the ____ protein, which activates it. Next, the ____ ____ ____ (___) activates _____ activity of the activated subunit, which causes it to hydrolyze ____ to ____ and become inactivated.

A
Conformational
G protein
Conformational 
Alpha 
GDP
GTP
Effector
GTPase Activating Protein (GAP)
GTPase 
GTP 
GDP
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44
Q

What are the names of the 3 subunits in a heterotrimeric G protein? Which subunits are required for binding to the G protein coupled receptor? Which two have functions different from the third? Which subunit has GTPase activity?

A

Alpha, beta, gamma
All 3
Beta and gamma
Alpha

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45
Q

Can the G protein coupled receptor activate more than 1 G protein as long as the ligand is bound?

A

Yes

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46
Q

Is GDP removal from the G protein a slow or fast process?

A

Slow

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47
Q

Is adding GTP to the G protein a slow or fast process?

A

Fast

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48
Q

How does the activated G protein coupled receptor affect the rate of G protein activation?

A

Speeds it up

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49
Q

Trimeric and monomeric G proteins are only active when?

A

When bound to GTP

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50
Q

Each G protein coupled receptor binds how many type(s) of G protein?

A

1

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51
Q

Which is considered to be an amplification step: the neurotransmitter binding to receptor, or the receptor binding to G protein? Why?

A

Receptor binding to G protein

Receptor can activate multiple G proteins per neurotransmitter bound

52
Q

What are the 3 types of heterotrimeric G proteins?

A

Gs, Gi, Gq

53
Q

Gs and Gi trimeric G proteins act on the effector protein ____ _____. Which one triggers inhibition, and which one triggers stimulation?

A

Adenylyl cyclase
Gs- stimulation
Gi- inhibtion

54
Q

Following binding to a Gs or Gi coupled receptor and activation of the corresponding G protein, adenylyl cyclase turns ____ into ____, which acts on ____ ____ ___, which _____ proteins.

A

ATP
cAMP
Protein kinase A
Phosphorylates

55
Q

Gq trimeric G proteins (activate/inhibit) the effector protein _____ ____.

A

Activate

Phospholipase C

56
Q

Following binding to a Gq coupled receptor and activation of the corresponding G protein, phospholipase C turns ______ into ____ and _____.

A

PIP2
DAG
IP3

57
Q

In the Gq trimeric protein pathway, DAG acts on ____ ____ ____ and IP3 stimulates _____ release by binding to a ligand-gated ion channel. Release of this ion acts on ___ ____ ____ (same as above) and ____ ____ ___.

A

Protein kinase C
Ca+2
Protein kinase C
Calcium calmodulin kinase

58
Q

Both the Gs and Gq trimeric G proteins _____ protein phosphorylation, whereas the Gi protein _____ it. In addition, the Gq protein activates ____-binding proteins.

A

Increase
Decreases
Calcium

59
Q

With Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), the (G protein coupled receptor/G protein) is mutated so that it cannot bind endogenous ligands. Instead, it binds the artificial ligand ____-___-____ (___). The (G protein coupled receptors/G proteins) still bind normally.

A

G protein coupled receptor
Clozapine-N-oxide (CNO)
G protein

60
Q

A given neurotransmitter can bind (one/ more than one) type of G protein coupled receptor. In contrast, a G protein coupled receptor can bind (one/ more than one) type of trimeric G protein. The trimeric G protein can bind (one/any) G protein coupled receptor with the appropriate intracellular domain.

A

More than one
One
Any

61
Q

A GTPase activating protein (GAP) activates the ___ activity of the ____ subunit of the trimeric G protein.

A

GTPase

Alpha

62
Q

A GTPase activating protein (GAP) has what effect on the alpha subunit’s ability to interact with the effector protein? Why?

A

Prevents it

Turns off alpha subunit by inducing hydrolysis of GTP to GDP

63
Q

How does the GTPase activating protein (GAP) moderate the effect of ligand binding to G protein coupled receptors? Can it turn off signaling even when ligand is still bound to the G protein coupled receptor?

A

Reduces

Yes

64
Q

A GTP exchange factor (GEF) enables the ____ subunit of the trimeric G protein to exchange ___ for ____.

A

Alpha
GDP
GTP

65
Q

A GTP exchange factor (GEF) has what effect on the alpha subunit’s ability to interact with the effector protein? Why?

A

Enables it

Turns on alpha subunit by replacing GDP with GTP

66
Q

How does the GTP exchange factor (GEF) moderate the effect of ligand binding to G protein coupled receptors? Can it turn on signaling in the absence of ligand?

A

Increases

Yes

67
Q

Both GTPase activating proteins (GAPs) and GTP exchange factors (GEFs) uncouple G protein ____ from ____ binding.

A

Signaling

Ligand

68
Q

The G protein coupled receptor itself acts as a (GAP/GEF) because it activates the G protein.

A

GEF

69
Q

Reduction of signaling by the alpha subunit of a trimeric G protein can be accomplished by increasing (GAP/GEF) activity and (GTPase activity/GTP binding).

A

GAP

GTPase activity

70
Q

Increased signaling by the alpha subunit of a trimeric G protein can be accomplished by increasing (GAP/GEF) activity and (GTPase activity/GTP binding).

A

GEF

GTP binding

71
Q

Dopamine has what 2 G protein coupled receptors? Which one couples to Gs and which one couples to Gi?

A

D1R (Gs)

D2R (Gi)

72
Q

When dopamine binds to a D1 receptor, protein X is phosphorylated. Which kinase is likely phosphorylating protein X? (Think about adenylyl cyclase pathway.)

A

Protein kinase A

73
Q

In the adenylyl cyclase pathway, _____ breaks down cyclic AMP.

A

Phosphodiesterase

74
Q

Which is the most important neuronal second messenger?

A

Ca+2

75
Q

5 neuronal second messengers

A
Ca+2
Cyclic AMP (cAMP)
Cyclic GMP (cGMP)
IP3
Diacylglycerol (DAG)
76
Q

What are two plasma membrane-based sources of Ca+2?

A

Voltage-gated Ca+2 channels

Various ligand-gated channels

77
Q

What are two endoplasmic reticulum-based sources of Ca+2?

A

IP3 receptors

Ryanodine receptors

78
Q

6 intracellular targets for Ca+2

A
Calmodulin
Protein kinases
Protein phosphatases
Ion channels
Synaptotagmin
Other Ca+2 binding proteins
79
Q

2 plasma membrane-based removal mechanisms for Ca+2

A

Na+/Ca+2 exchanger

Ca+2 pump

80
Q

1 endoplasmic reticulum based removal mechanism for Ca+2

A

Ca+2 pump

81
Q

Organelle (in addition to endoplasmic reticulum) that is involved in removal of Ca+2

A

Mitochondria

82
Q

Source of cAMP: ____ ____ acts on ____

A

Adenylyl cyclase

ATP

83
Q

2 intracellular targets of cAMP

A

Protein kinase A

Cyclic nucleotide-gated channels

84
Q

What enzyme is responsible for removal of cAMP?

A

cAMP phosphodiesterase

85
Q

Source of cGMP: ____ ____ acts on ____

A

Guanylyl cyclase

GTP

86
Q

2 intracellular targets of cGMP

A

Protein kinase G

Cyclic nucleotide-gated channels

87
Q

What enzyme is responsible for removal of cGMP?

A

cGMP phosphodiesterase

88
Q

Source of IP3: ______ ____ acts on _____

A

Phospholipase C

PIP2

89
Q

Intracellular target of IP3 (molecule type, location)

A

IP3 receptors on endoplasmic reticulum

90
Q

What type of enzyme is responsible for removal of IP3?

A

Phosphatase

91
Q

Source of diacylglycerol (DAG): ____ ____ acts on _____ (same as for IP3)

A

Phospholipase C

PIP2

92
Q

Intracellular target of diacylglycerol (DAG)

A

Protein kinase C

93
Q

Removal of diacylglycerol (DAG): various ____

A

Enzymes

94
Q

4 types of proteins regulated by binding Ca+2 and what they do

A

Protein kinase C (phosphorylates)
Calcineurin (phosphatase- dephosphorylates)
Calmodulin (Ca+2 buffering, activates CaMKII)
Calcium calmodulin kinase II (CaMKII; phosphorylates)

95
Q

2 targets of CaMKII (talked about earlier in lecture; many more targets than just these 2)

A

GAPs

GEFs

96
Q

cAMP and cGMP are both considered ____ _____. They target what type of channels? On which side of the channels do they bind? Both activate a protein _____.

A

Cyclic nucleotides
Cyclic nucleotide gated channels
Cytoplasmic side
Kinase

97
Q

PIP2 is the precursor of both _____ and _____.

A

Diacylglycerol

IP3

98
Q

PIP2 and diacylglycerol (DAG) are both located in the ____ ____. What enzyme breaks PIP2 down into DAG?

A

Plasma membrane

Phospholipase C

99
Q

While PIP2 is located in the plasma membrane, IP3 is located in the _____. IP3 binds the IP3 receptor, a ligand-gated ion channel for what ion?

A

Cytosol

Ca+2

100
Q

_____ (enzyme type) breaks IP3 into _____.

A

Phosphatases

Inositol

101
Q

Most enzymes are regulated so that they have ____ or ____ forms. Why is this?

A

Active
Inactive
Easier to inactivate or activate enzyme than to synthesize it every time it is needed

102
Q

Regulation of enzyme activity is usually accomplished by binding to ____ ____ and/or altering the _____ state of the enzyme.

A

Second messengers

Phosphorylation

103
Q

Activating conformational change of an enzyme will separate its _____ and _____ domains/subunits.

A

Catalytic

Regulatory

104
Q

What part of the enzyme has enzymatic activity? What part inhibits the enzyme?

A

Catalytic

Regulatory

105
Q

Regulatory and catalytic parts of enzyme: domains of same protein, separate protein subunits, or either?

A

Either

106
Q

Protein kinase A has how many regulatory subunits? How many catalytic subunits?

A

2

2

107
Q

What molecule activates protein kinase A? How many molecules per regulatory subunit?

A

cAMP

2 molecules per subunit, 4 total

108
Q

How is protein kinase A activated?

A

4 molecules of cAMP bind to regulatory subunits (2 per subunit), which triggers conformational change that activates protein kinase A

109
Q

Ca+2 calmodulin kinase II (CaMKII) has how many regulatory domains? How many catalytic domains?

A

6

6

110
Q

For protein kinase A and calcineurin, each subunit comes from a separate _____.

A

Protein

111
Q

What 2 molecules activate CaMKII?

A

Ca+2

Calmodulin

112
Q

In the absence of Ca+2 and calmodulin, what does CaMKII look like? After activation, how does its shape change?

A

Folded up

Opens up

113
Q

How is CaMKII activated?

A

Ca+2 and calmodulin bind to CaMKII, causing a conformational change that opens it up and activates it

114
Q

How many regulatory domains does protein kinase C have? How many catalytic domains?

A

2

1

115
Q

What 2 molecules activate protein kinase C?

A

Ca+2

Diacylglycerol (DAG)

116
Q

How is protein kinase C activated?

A

Ca+2 and DAG interact with regulatory domains (located near plasma membrane, since DAG is plasma membrane bound), which triggers conformational change that activates protein kinase C

117
Q

MAP kinases are activated by _____, which involves covalently binding a _____ group from _____.

A

Phosphorylation
Phosphate
ATP

118
Q

2 ways that MAP kinases are phosphorylated (and thus activated)

A

Auto-phosphorylation

Phosphorylation by other kinases

119
Q

The phosphatase calcineurin requires which 2 molecules to become activated? What kinase is activated in a similar way?

A

Ca+2
Calmodulin
CaMKII

120
Q

cAMP Response Element Binding (CREB) has what function?

A

Transcription factor

121
Q

What effect does CREB have on transcription? (Increase, decrease, either)

A

Either increases or decreases

122
Q

CREB is activated by ____ through many different ____. What is the name of the active form found in the nucleus that binds DNA?

A

Phosphorylation
Kinases
pCREB (phosphorylated CREB)

123
Q

CREB can be activated through G-protein mediated activation of ____ ____, which activates ____, which activates ___ ___ ___, which phosphorylates CREB. CREB can also be activated by ____, which enters through ion channels and activates ____ ____ ____ or _____ ____, either of which can phosphorylate CREB.

A
Adenylyl cyclase
cAMP
Protein kinase A
Ca+2
Calcium calmodulin kinase
MAP kinase
124
Q

Of the 4 types of cellular receptors, which one has direct phosphatase and kinase abilities?

A

Enzyme-linked receptors

125
Q

In the G-protein pathway, what are the 3 amplification steps?

A

Receptor activates G protein
Effector protein activates second messengers
Later effectors (protein kinases, etc.) perform target action (phosphorylation, etc.)

126
Q

(GAPs/GEFs) promote dissociation of G protein subunits, whereas (GAPs/GEFs) promote re-association of G protein subunits. (Remember which is associated with activation and which is associated with inactivation)

A

GEFs

GAPs

127
Q

What kinase is active in long-term depression (LTD), and which is active in long-term potentiation (LTP)? These kinases phosphorylate which 2 receptors? What is the effect of phosphorylation in LTD and what is the effect of phosphorylation in LTP?

A
LTD: protein kinase C
LTP: CaMKII
AMPA, NMDA
LTD: decreased depolarization
LTP: increased depolarization