Intracellular Signal Transduction Flashcards Preview

Neurobiology > Intracellular Signal Transduction > Flashcards

Flashcards in Intracellular Signal Transduction Deck (24):
1

Three stages of cell signaling

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

2

Chemical signaling mechanisms

1. Synaptic signaling
2. Paracrine
3. Endocrine

3

Paracrine

Secrete molecules act locally
Do not diffuse far

4

Endocrine

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

5

Signaling cascade

signaling cell
signal
receptor
target molecule
molecule

6

Three classes of cell signaling molecules

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

7

Categories of cellular receptors

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

8

effector pathways associated with g-protein

1. norepinephrine
2. glutamate
3. dopamine

9

G-protein cascade of Norepinephrine

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

10

G-protein cascade of Glutamate

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

11

G-protein cascade of Dopamine

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

12

Receptor tyrosine kinases (RTK)

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

13

RTK

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

14

Ca2+ as a second messenger - Source

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

15

Ca2+ as a second messenger - Intracellular targets

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

16

Ca2+ as a second messenger - Removal mechanism

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

17

Neuronal 2nd messengers - Cyclic AMP

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

cyclic nucleotide pathway

18

Neuronal 2nd messengers - Cyclic GMP

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

cyclic nucleotide pathway

19

Neuronal 2nd messengers - IP_3

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

Neuronal 2nd messengers - Diacylglycerol

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

21

Phosphorylation

Protein kinases and phosphatases

Protein kinases: add phosphate to proteins
Phosphatases remove

22

Protein kinases; PKA

cAMP dependent serine/threonine kinase
majority of cAMP's affect mediated by PKA

23

Ca2+/calmodulin-dependent kinase II -- CaMKII

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

PKC

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