Cell Communication

1
Chapter 15

• Cell Communication

2
Intracellular signaling pathway triggered by
extracellular signal molecule
3

• Two types of signaling pathways
• Cell surface receptors
• Intracellular (nuclear) receptors
• Signal Concentration
• lt 10-8M
• Receptor Affinity
• K? lt10-8 M/L

4
Forms of intercellular signaling
5
Signal Coordination

• Autocrine signaling coordinates groups of
  identical cells
• Gap junctions can also function to coordinate
  responses

6

• Endocrine signaling
• Short/long term
• Specificity by ligand binding
• Synaptic signaling
• Spatial specificity
• Same ligand

7
Signals can act rapidly or slowly to affect a
target cell.
8
Cells integrate multiple signals to control
different processes
9

• A single signal can affect different cells in
  different ways

10
Cells adopt different fates depending upon their
position in a morphogen gradient.
11
Importance of rapid signal turnover

• Red molecule turned over quickly
• Green molecule turned over slowly
• Half-lives

12
The role of NO gas in smooth muscle relaxation in
a blood vessel wall
13

• Two types of signaling pathways
• Cell surface receptors
• Intracellular (nuclear) receptors
• Signal Concentration
• lt 10-8M
• Receptor Affinity
• K? lt10-8 M/L

14

• Members of the steroid hormone superfamily of
  hormones
• Insects Ecdysteroids and Juvenile Hormones

15
Nuclear receptor superfamily

• Receptors act as dimers
• Heterodimers
• Homodimers

16
Ligand binding domain

• Ligand binding causes conformational change
• Traps ligand

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Chromosome Puffs!
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Puffs activated following ecdysteroid stimulation
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Puff shows RNA synthesis
3H uridine staining
21

• Two types of signaling pathways
• Cell surface receptors
• Intracellular (nuclear) receptors
• Signal Concentration
• lt 10-8M
• Receptor Affinity
• K? lt10-8 M/L

22
3 classes of cell surface receptors
23
Receptor deactivation regulates cell sensitivity
24

• Different kinds of proteins involved in cell
  signaling
• Relay proteins
• Scaffold proteins link signaling proteins
  together
• Transducer proteins convert signal
• Amplifier proteins increase signal strength
• Integrator proteins receive several signals
• Bifurcation proteins spread signal from one
  pathway to another
• Messenger proteins carry signal throughout cell

25
Cells integrate multiple signals to control
different processes
26
Two types of intercellular signaling proteins
that act as molecular switches
27
Signal Integration-coincidence detectors
28
Signaling complexes
Enhance the speed, efficiency and specificity of
the response
29
3 classes of cell surface receptors
30
G-Protein linked signaling
G-Protein Receptor
31
The disassembly of an activated G-Protein into
two signaling components
32
The G-Protein a-subunit hydrolyses its bound GTP
to turn itself off.

• Both subunits can activate downstream processes
• G-Proteins activate second messenger systems
• cAMP synthesis
• Diacylglycerol/IP3 synthesis

33
G-Protein action- Second messenger 1. Some
G-Proteins increase cAMP levels

• Nerve cell responding to serotonin acting via a
  G-protein linked to cAMP levels

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Enzymes regulating cAMP levels

• Adenylyl cyclase (On)
• Makes cAMP from ATP
• cAMP phosphodiesterase (Off)
• Breaks cAMP down to 5-AMP

36
Multiple subunits increase abruptness of response
37
cAMP stimulates protein kinase A

• Example of a multi-ligand switch
• Increases sensitivity to increasing cAMP levels

38
In some cases, cAMP can mediate gene transcription
PKA modes of action

• PKA activates CRE-binding protein (CREB)
• Recruits CREB binding protein (CBP)
• CREB/CBP complex binds to CRE
• cAMP Response Element (CRE)

39

• G-Protein action- Second messenger
• 2. Some G-Proteins can activate Phospholipase-C
  (PLC)

40
Phospholipase-C

• Membrane bound
• PLC hydrolyses phosphotidylinositol
  4,5-bisphosphate (PIP2) to
• DAG (lipid soluble)
• Activates Protein Kinase C
• IP3 (cytosolic)
• Triggers calcium release from ER

41
The two branches of the inositol phosphate
signaling pathway
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• Calcium as a messenger
• Eukaryotic cells maintain low cytosolic Ca2
  concentration
• Pump Ca2 out of cell
• Ca2binding molecules
• Pump Ca2 into ER or mitochondria

44
Starfish egg at point of fertilization
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Vasopressin induced Ca2 release in liver cell
46
Vasopressin induced Ca2 release in liver
cell Oscillation frequency can affect gene
transcription
47
Calmodulin is the calcium receptor
48
CaM-Kinase II (Calcium/calmodulin dependent
kinase)
CaM-Kinase has memory
49
Summation of response
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Smell and vision depend on G-protein linked
receptors that regulate cyclic nucleotide gated
ion channels
Cyclic GMP
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Receptor deactivation regulates cell sensitivity
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Arrestin desensitizes G-protein linked receptor
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3 classes of cell surface receptors
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Receptor tyrosine kinases
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Activation of Ras by receptor tyrosine kinase
60
Ras activates MAP-kinases Mitogen-activated
protein kinase
MAP KKK Raf MAP KK Mek MAP K Erk
61
Five parallel intracellular signaling pathways
activated by G-protein-linked receptors, receptor
tyrosine kinases, or both.
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