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Neurobiology > Intracellular Signal Transduction > Flashcards

Intracellular Signal Transduction Flashcards

1
Q

Three stages of cell signaling

A
  1. reception 2. transduction 3. response (protein/enzyme function, gene transcription)
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2
Q

Chemical signaling mechanisms

A
  1. Synaptic signaling
  2. Paracrine
  3. Endocrine
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3
Q

Paracrine

A

Secrete molecules act locally

Do not diffuse far

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4
Q

Endocrine

A

Hormone signaling
some distance away
carried by the blood/extracellular fluids

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5
Q

Signaling cascade

A 
signaling cell
signal
receptor
target molecule
molecule
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6
Q

Three classes of cell signaling molecules

A
  1. cell-impermeant molecules; need transmembrane receptor
  2. Cell-permeant molecules; intracellular receptor
  3. cell-associated molecules; come in contact with receptor
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7
Q

Categories of cellular receptors

A
  1. channel-linked receptor; channel opens
  2. enzyme-linked receptor; enzyme generates product
  3. G-protein-coupled receptor; activates G-protein
  4. Intracellular receptor; activated receptor regulates transcription
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8
Q

effector pathways associated with g-protein

A
  1. norepinephrine
  2. glutamate
  3. dopamine
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9
Q

G-protein cascade of Norepinephrine

A

Neurotransmitter: norepinephrine (increases)
receptor: beta-adrenergic
g-protein: G_s
Effector protein: Adenylyl cyclase
Second Messenger: cAMP
Later effectors: Protein kinase A
Target action: Increase protein phosphorylation

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10
Q

G-protein cascade of Glutamate

A 
Neurotransmitter: glutamate
Receptor: mGluR
G-protein: G_q
Effector protein: Phospholipase C
Second messenger 1: Diacylglycerol
Later effector 1: Protein kinase C
Second messenger 2: IP_3
Later effector 2: Ca2+ release
Target action: Increase protein phosphorylation and activate calcium binding proteins
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11
Q

G-protein cascade of Dopamine

A 
Neurotransmitter: Dopamine (decrease)
receptor: Dopamine D2
g-protein: G_i
Effector protein: Adenylyl cyclase
Second Messenger: cAMP
Later effectors: Protein kinase A
Target action: Increase protein phosphorylation
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12
Q

Receptor tyrosine kinases (RTK)

A

involved in cell proliferation, differentiation, survival - ligand(growth factor); NGF
Three domains: extracellular ligand binding domain;transmembrane domain; cytosolic protein kinase domain
poor kinase activity

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13
Q

RTK

A

Receptor Tyrosine Kinases
Ligand bind -> dimerize
kinase domain of one monomer phosphorylates the other; tyrosine in the activation lip
kinase activity now enhanced;additional tyrosines on the receptor phosphorylated; lead to binding of other proteins or ATP

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14
Q

Ca2+ as a second messenger - Source

A 
Source: 
Plasma membrane (Voltage gated Ca2+ channels, various ligand gated channels)
Endoplasmic Reticulum (IP_3 receptors, Ryanodine receptor)
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15
Q

Ca2+ as a second messenger - Intracellular targets

A

Intracellular targets (Calmodulin, Protein kinases, Protein phosphatases, Ion channels, Synaptotagmin, Many other Ca2+ binding proteins)

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16
Q

Ca2+ as a second messenger - Removal mechanism

A 
Removal mechanism:
Plasma membrane (Na+/Ca2+ exchanger, Ca2+ pump)
Endoplasmic Reticulum (Ca2+ pump)
Mitochondria
17
Q

Neuronal 2nd messengers - Cyclic AMP

A

Source: Adenylyl cyclase on ATP
Intracellular target: PKA, Cyclic nucleotide-gated channels
Removal mechanism: cAMP phosphodiesterase

cyclic nucleotide pathway

18
Q

Neuronal 2nd messengers - Cyclic GMP

A

Source: Guanylyl cyclase on GTP
Intracellular target: PKG, Cyclic nucleotide-gated channels
Removal mechanism: cGMP phosphodiesterase

cyclic nucleotide pathway

19
Q

Neuronal 2nd messengers - IP_3

A

Source: Phospholipase C (PLC) on PIP_2
Intracellular target: IP_3 receptors on ER
Removal mechanism: Phosphatases

IP_3 pathway; Ca2+ release increased from ER; increased Ca2+ activate PKC
DAG pathway; DAG(diacylglycerol) level activates PKC;

20
Q

Neuronal 2nd messengers - Diacylglycerol

A

Source: Phospholipase C on PIP_2
Intracellular targets: PKC
Removal mechanism: various enzymes

21
Q

Phosphorylation

A

Protein kinases and phosphatases

Protein kinases: add phosphate to proteins
Phosphatases remove

22
Q

Protein kinases; PKA

A

cAMP dependent serine/threonine kinase

majority of cAMP’s affect mediated by PKA

23
Q

Ca2+/calmodulin-dependent kinase II – CaMKII

A

most abundant kinase
Ca2+ binds to calmodulin & displaces inhibitory domain from a catalytic domain (i.e. activates it)
regulates a lot of signal transduction proteins and ion channels
serine/threonine kinase

24
Q

PKC

A 
monomeric kinase
activated by DAG and Ca2+
DAG brings PKC to membrane
Ca2+ and phosphatidylserine bind
age - PKC activity reduced; Alzheimer's Disease

Neurobiology (11 decks)

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