Molecular Signaling within Neurons Flashcards

1
Q

Signal amplification across several steps in a cascade is _____.

A

exponential

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2
Q

Extracellular signaling molecules:

A
  • Small soluble organic molecules e.g. Neurotransmitters, amino acids, sugars, nucleotides
  • Inorganic ions (e.g. Zn2+)
  • Diffusable gases (e.g. CO & NO)
  • Peptides
  • Lipophilic organic molecules (e.g. endocannabinoids)
  • Cell-surface expressed proteins
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3
Q

Cholesterol derived hormones are ____ molecules.

A

cell permeant

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4
Q

Cell-cell adhesion molecules require _____.

A

direct contact

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5
Q

metabotropic receptors are proteins consisting of ___.

A

7 transmembrane domains

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6
Q

Domains _____ make up the neurotansmitter binding region of metabotropic receptors.

A

II, III, VI, and VII

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7
Q

G-proteins bind to both the loop between domains _ and _ and the _____.

A

V
VI
C-terminus

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8
Q

Ras are small ____.

A

GTPases

bind and accelerate hydrolyzation of guanosine triphosphate

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9
Q

Heterotrimeric G-proteins are “_____.”

A

large

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10
Q

There are several classes of Gα subunits:

A

G(s)α (stimulatory)
G(i)α (inhibitory)
G(q)α (activates phospholipase C)

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11
Q

Proteins called GTPase-activating proteins (GAPs) accelerate the _____.

A

hydrolisis of GTP to GDP

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12
Q

Monomeric G-proteins are known as “_____.”

A

small G-proteins

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13
Q

“Small” G proteins belong to the _____ of small GTPases.

A

Ras superfamily

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14
Q

Monomeric proteins are homologous to the _____ found in heterotrimers.

A

alpha (α) subunit

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15
Q

A small GTPase can function independently as a _____ to bind to and hydrolyze _____.

A

hydrolase enzyme

GTP to form GDP

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16
Q

Two principal signal transduction pathways of G protein-coupled receptors:

A

1) Adenylyl cyclase – cAMP signal pathway (via G(α-s) and G(α-i))
2) Phospholipase C signal pathway (via G(α-q))

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17
Q

Activation of adenylate cyclase (via G(s-α) or G(i-α) leads to:

A
  • cAMP formation

* protein kinase A (PKA)

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18
Q

The adenylyl cyclase (cAMP signal) pathway through B-adrenergic GPCR _____.

A

increases protein phosphorylation

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19
Q

The adenylyl cyclase (cAMP signal) pathway through DA(2) GPCR _____.

A

decreases protein phosphorylation

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20
Q

The Phospholipase C signal pathway through mGluR _____.

A

increases protein phosphorylation

activates calcium-binding proteins

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21
Q

Upon binding of the alpha subunit of the G-protein, _____ catalyzes the conversion of ATP to _____.

A

adenylate cyclase

3’,5’-cyclic AMP (cAMP)

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22
Q

G(α-s) and G(α-i) oppose each other through their modulation of _____.

A

adenylyl cyclase activity

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23
Q

Binding of G(α-s) (via D1 receptors) to AC _____ the synthesis of cAMP.

A

increases

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24
Q

Binding of G(α-i) (via D2 receptors) to AC _____ the synthesis of cAMP

A

decreases

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25
5-HT (via a metabotropic receptor) activates _____ which in turn increases cAMP, and then _____.
Adenylyl-cyclase | PKA
26
PKA has 2 effects:
* Closes K+ channels, leading to broader spikes and more Ca2+ influx (more transmitter release) * PKA directly increases the release of neurotransmitter
27
G-protein coupled receptors (G(α-q)) activate _____.
PLC
28
PLC cleaves PIP2 into _____ and _____.
inositol -1,4,5-triphosphate (IP3, soluble) | diacylglycerol (DAG, membrane bound)
29
IP3 stimulates the release of _____ from the endoplasmic reticulum.
calcium ions
30
DAG is an activator of _____ which stimulates the release of calcium ions through a _____.
protein kinase C (PKC) | Ca2+ channel
31
Under baseline conditions, the cytosol is largely kept _____ of Ca2+
devoid
32
Ca2+ as a secondary messenger is either pumped out of the cell, sequestered in internal stores in the _____ and _____, or bound by _____.
ER lumen mitochondrial matrix calcium-binding proteins
33
_____ and _____ receptors in the ER membrane allow flow of Ca2+ from internal stores into the _____.
IP3 ryanodine cytosol
34
As a messenger, Ca2+ targets:
Calmodulin Protein kinases Ion chennels Synaptotagmin
35
cAMP (acronym):
Cyclic adenosine monophosphate
36
cAMP is synthezised from ATP by _____.
adenylyl cyclase
37
An increase in cAMP leads to activation of _____.
Protein kinase A (PKA)
38
Removal mechanism of cAMP
cAMP phosphodiesterase
39
Removal mechanism of IP(3)
Phosphatases
40
Protein Kinases
enzymes that are the effectors of phosphorylation and catalyze the transfer of a phosphate group from ATP to specific amino acids on proteins.
41
Proteins are phosphorylated predominantly on ______, _____, and _____ residues.
Serine Threonine Tyrosine
42
types of protein kinases
Serine/Threonine kinases | Tyrosine Kinases
43
Protein Phosphatases
enzymes that cleave phosphate from target molecule | dephosphorylate
44
_____ are responsible for transferring phosphate groups to target proteins.
Catalytic subunits
45
Catalytic subunits are being kept inactive by _____.
regulatory subunits (autoinhibition)
46
Binding of the second messenger (cAMP; DAG; Ca2+) removes _____ and allows ______ to be activated.
autoinhibition | catalytic domain
47
cAMP activates PKA by binding to the _____ and causing them to release active _____.
regulatory subunits | catalytic subunits
48
Catalytic subunits phosphorylate_____ and _____ of target proteins after activation.
serine | threonine residues
49
DAG (Diacylglycerol) causes _____ to move from the cytosol to the membrane where it binds ____ and another _____.
PKC Ca2+ phospholipid (PS)
50
binding of _____ to PKC relieves autoinhibition, enabling PKC to phosphorylate proteins.
DAG
51
CaMKII (acronym):
Ca2+/calmodulin dependent protein kinase type II
52
On CaMKII, calcium binds to _____.
calmodulin
53
Ca2+/calmodulin activates CaMKII by displacing _____ from the _____.
the inhibitory domain | catalytic subunit
54
At least 2 Ca2+-activated protein kinases are responsible for LTP:
* Ca2+/calmodulin-dependent protein kinase II (CaMKII), and | * Protein kinase C (PKC)
55
Expression (maintenance) of LTP is typically due to insertion of _____ into the _____ membrane (increasing the response to glutamate)
AMPA-Rs | postsynaptic
56
MAPK (acronym):
Mitogen-activated protein kinase
57
MAPK [specifically the extracellular signal-regulated kinase (ERK) subfamily]
Phosphorylate transcription factors | proteins that regulate gene expression
58
Late LTP is induced by changes in _____ and _____ brought about by the persistent activation of protein kinases activated during early-LTP, such as _____.
gene expression protein synthesis MAPK
59
Many signaling cascades involved in early-LTP, including CaMKII and PKC, can converge on _____.
ERK
60
Upon activation, ERK phosphorylates transcription factors such as _____, leading to _____.
CREB | synthesis of new proteins
61
Cascades can _____ at G-proteins to produce different effector proteins or _____ at effector/G-proteins to produce one kind of effector protein.
diverge | converge
62
______ are the primary effectors of dephosphorylation and act in opposition to ______.
Protein phosphatases | protein kinases
63
The largest class of ______ is the phosphoprotein phosphatase family, which –among others– contains __, __, and __.
PPs (protein phosphatases) PP-1 PP-2A PP-2B (calcineurin)
64
Several proteins have _____ for activating or inhibiting functional regulation.
separate phosphorylation sites
65
The amount of protein present in cells is determined by the rate of _____.
transcription of DNA into RNA
66
Transcription factors allow _____ to assemble on the _____ and to begin transcription.
RNA polymerase | DNA promoter region
67
Transcription factors either stimulate or inhibit _____ activity.
RNA polymerase | transcriptional activator protein
68
Transcriptional Activators
enhance gene expression
69
Transcriptional Repressors
decrease gene expression
70
CREB (acronym):
cAMP response element-binding protein
71
CREB is a _____.
cellular transcription factor
72
CREB binds to DNA sequences called _____, thereby increasing or decreasing the transcription of the downstream genes.
cAMP response elements (CRE)
73
CREB is normally _____.
unphosphorylated
74
CREB's phosphorylation potentiates _____.
transcription
75
Activators of CREB:
* PKA * Ras / MAPK pathway * CaMK-IV (a variant of CaMK-II) * Ca2+
76
Important genes transcribed by CREB:
* c-fos (an immediate early gene that itself acts as transcription factor for other genes) * the neurotrophic factor BDNF * tryosine hydroxylase * neuropeptides