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Cellular Neuroscience > Molecular Signaling within Neurons > Flashcards

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
Q

5-HT (via a metabotropic receptor) activates _____ which in turn increases cAMP, and then _____.

A

Adenylyl-cyclase

PKA

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26
Q

PKA has 2 effects:

A
  • Closes K+ channels, leading to broader spikes and more Ca2+ influx (more transmitter release)
  • PKA directly increases the release of neurotransmitter
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27
Q

G-protein coupled receptors (G(α-q)) activate _____.

A

PLC

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28
Q

PLC cleaves PIP2 into _____ and _____.

A

inositol -1,4,5-triphosphate (IP3, soluble)

diacylglycerol (DAG, membrane bound)

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29
Q

IP3 stimulates the release of _____ from the endoplasmic reticulum.

A

calcium ions

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30
Q

DAG is an activator of _____ which stimulates the release of calcium ions through a _____.

A

protein kinase C (PKC)

Ca2+ channel

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31
Q

Under baseline conditions, the cytosol is largely kept _____ of Ca2+

A

devoid

32
Q

Ca2+ as a secondary messenger is either pumped out of the cell, sequestered in internal stores in the _____ and _____, or bound by _____.

A

ER lumen
mitochondrial matrix
calcium-binding proteins

33
Q

_____ and _____ receptors in the ER membrane allow flow of Ca2+ from internal stores into the _____.

A

IP3
ryanodine
cytosol

34
Q

As a messenger, Ca2+ targets:

A

Calmodulin
Protein kinases
Ion chennels
Synaptotagmin

35
Q

cAMP (acronym):

A

Cyclic adenosine monophosphate

36
Q

cAMP is synthezised from ATP by _____.

A

adenylyl cyclase

37
Q

An increase in cAMP leads to activation of _____.

A

Protein kinase A (PKA)

38
Q

Removal mechanism of cAMP

A

cAMP phosphodiesterase

39
Q

Removal mechanism of IP(3)

A

Phosphatases

40
Q

Protein Kinases

A

enzymes that are the effectors of phosphorylation and catalyze the transfer of a phosphate group from ATP to specific amino acids on proteins.

41
Q

Proteins are phosphorylated predominantly on ______, _____, and _____ residues.

A

Serine
Threonine
Tyrosine

42
Q

types of protein kinases

A

Serine/Threonine kinases

Tyrosine Kinases

43
Q

Protein Phosphatases

A

enzymes that cleave phosphate from target molecule

dephosphorylate

44
Q

_____ are responsible for transferring phosphate groups to target proteins.

A

Catalytic subunits

45
Q

Catalytic subunits are being kept inactive by _____.

A

regulatory subunits (autoinhibition)

46
Q

Binding of the second messenger (cAMP; DAG; Ca2+) removes _____ and allows ______ to be activated.

A

autoinhibition

catalytic domain

47
Q

cAMP activates PKA by binding to the _____ and causing them to release active _____.

A

regulatory subunits

catalytic subunits

48
Q

Catalytic subunits phosphorylate_____ and _____ of target proteins after activation.

A

serine

threonine residues

49
Q

DAG (Diacylglycerol) causes _____ to move from the cytosol to the membrane where it binds ____ and another _____.

A

PKC
Ca2+
phospholipid (PS)

50
Q

binding of _____ to PKC relieves autoinhibition, enabling PKC to phosphorylate proteins.

A

DAG

51
Q

CaMKII (acronym):

A

Ca2+/calmodulin dependent protein kinase type II

52
Q

On CaMKII, calcium binds to _____.

A

calmodulin

53
Q

Ca2+/calmodulin activates CaMKII by displacing _____ from the _____.

A

the inhibitory domain

catalytic subunit

54
Q

At least 2 Ca2+-activated protein kinases are responsible for LTP:

A
  • Ca2+/calmodulin-dependent protein kinase II (CaMKII), and

* Protein kinase C (PKC)

55
Q

Expression (maintenance) of LTP is typically due to insertion of _____ into the _____ membrane
(increasing the response to glutamate)

A

AMPA-Rs

postsynaptic

56
Q

MAPK (acronym):

A

Mitogen-activated protein kinase

57
Q

MAPK [specifically the extracellular signal-regulated kinase (ERK) subfamily]

A

Phosphorylate transcription factors

proteins that regulate gene expression

58
Q

Late LTP is induced by changes in _____ and _____ brought about by the persistent activation of protein kinases activated during early-LTP, such as _____.

A

gene expression
protein synthesis
MAPK

59
Q

Many signaling cascades involved in early-LTP, including CaMKII and PKC, can converge on _____.

A

ERK

60
Q

Upon activation, ERK phosphorylates transcription factors such as _____, leading to _____.

A

CREB

synthesis of new proteins

61
Q

Cascades can _____ at G-proteins to produce different effector proteins or _____ at effector/G-proteins to produce one kind of effector protein.

A

diverge

converge

62
Q

______ are the primary effectors of dephosphorylation and act in opposition to ______.

A

Protein phosphatases

protein kinases

63
Q

The largest class of ______ is the phosphoprotein phosphatase family, which –among others– contains __, __, and __.

A

PPs (protein phosphatases)
PP-1
PP-2A
PP-2B (calcineurin)

64
Q

Several proteins have _____ for activating or inhibiting functional regulation.

A

separate phosphorylation sites

65
Q

The amount of protein present in cells is determined by the rate of _____.

A

transcription of DNA into RNA

66
Q

Transcription factors allow _____ to assemble on the _____ and to begin transcription.

A

RNA polymerase

DNA promoter region

67
Q

Transcription factors either stimulate or inhibit _____ activity.

A

RNA polymerase

transcriptional activator protein

68
Q

Transcriptional Activators

A

enhance gene expression

69
Q

Transcriptional Repressors

A

decrease gene expression

70
Q

CREB (acronym):

A

cAMP response element-binding protein

71
Q

CREB is a _____.

A

cellular transcription factor

72
Q

CREB binds to DNA sequences called _____, thereby increasing or decreasing the transcription of the downstream genes.

A

cAMP response elements (CRE)

73
Q

CREB is normally _____.

A

unphosphorylated

74
Q

CREB’s phosphorylation potentiates _____.

A

transcription

75
Q

Activators of CREB:

A
  • PKA
  • Ras / MAPK pathway
  • CaMK-IV (a variant of CaMK-II)
  • Ca2+
76
Q

Important genes transcribed by CREB:

A
  • c-fos (an immediate early gene that itself acts as transcription factor for other genes)
  • the neurotrophic factor BDNF
  • tryosine hydroxylase
  • neuropeptides

Cellular Neuroscience (13 decks)

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