LigandReceptor Interactions Cell and Developmental Biology Group Goals Integration of quantitative skills in cell biology Modeling cellular responses Class setup First or second year majors in cell biology ID: 569195
Download Presentation The PPT/PDF document "Signal Transduction:" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Signal Transduction:
Ligand-Receptor Interactions
Cell and Developmental
Biology GroupSlide2
Goals –
Integration of quantitative skills in cell biology
Modeling cellular responses
Slide3
Class setup
First or second year majors in cell biology
Co-requisite with Calculus
Middle of the course
~1 hour lecture
Learning outcomes
1) Relate the concept of threshold to cellular responses
2) Understand how these components affect threshold
- ligand and receptor concentrations
- binding affinity
3) Apply knowledge of quantitative models of cellular responseSlide4
A driver returned to his car after a 3 hour shopping spree to see the following sight. His car would not start. Why?Slide5
Battery current thresholds
Battery power
0%
100%Slide6
Draw how the battery / ignition threshold would look on this graph
Battery current
Response (ignition)
low
high
No ignition
ignitionSlide7
Cell Signaling
EXTRACELLULAR
FLUID
Reception
Receptor
Signal
molecule
Plasma membrane
Transduction
CYTOPLASM
Relay molecules in a signal transduction
pathway
Response
Activation
of cellular
response
Tomorrow’s presentationSlide8
What happens when you see this?Slide9
Effects of adrenaline on different tissues in the bodySlide10
Threshold as it relates to ligand
receptor binding and cellular function
Basic response threshold
Maximum response threshold
[Adrenaline]
Fight - Flight response
low
high
Ligand / receptor concept
ReceptionSlide11
1 Ligand receptor complex
100 - 1000 Ligand receptor complexes
1000 -10,000 Ligand receptor complexes
10,000 -100,000 Ligand receptor complexes
100,000 - 1 million Ligand receptor complexes
How many
ligand
/ receptor complexes are required to elicit a cellular response?Slide12
Binding Affinity
[L] + [R] [LR]
Dissociation Constant (K
d
): is the free ligand concentration at which 50% of receptor is occupied.
Affinity
is defined by the association constant (K
a
) =1/K
d
Each ligand / receptor complex has its own specific binding affinity.
k
1
k
-1
K
d
=
k
-1
/ k
1Slide13
[ligand]
response
Which graph represents a cell with a receptor with the highest affinity?
low
high
A
B
C
DSlide14
(Think-Pair 1 minute essay)
What is the relationship between affinity and threshold?
[ligand]
response
low
high
A
B
C
DSlide15
Affinity and the curves
Which of these factors can the cell control?
How might a cell be able to control its own threshold?
Affinity = 1 / K
dSlide16
Affinity and the curves
[Ligand]
Response
Affinity = 1 / K
d
Associate each of the following with the appropriate graph above
A. [L]=1 µM, [R]=0.5 µM, K
d
=.25 µM
[L]=1 µM, [R]=1.25 µM, K
d
=.25 µM
B
ASlide17
Affinity and the curves
[Ligand]
Response
Affinity = 1 / K
d
Associate each of the following with the appropriate graph above
A. [L]=1 µM, [R]=1.25 µM, K
d
=.25 µM
B. [L]=1 µM, [R]=1.25 µM, K
d
=.5 µM
A
BSlide18
Relationship between [R],[LR],Kd
In general,
What happens to [LR] when [R] increases and K
d
stays the same?
What happens to [LR] when K
d increases and [R] stays the same?Slide19
Affinity and the curves
[Ligand]
Response
Associate each of the following with the appropriate graph above
A. [L]=1 µM, [R]=0.5 µM, K
d
=.25 µM
[L]=1 µM, [R]=1.25 µM, K
d
=.25 µM
[L]=1 µM, [R]=1.25 µM, K
d
=.5 µM
Affinity = 1 / K
d
B
A
CSlide20
Affinity and the curves
[Ligand]
Response
Associate each of the following with the appropriate graph above
A. [L]=1 µM, [R]=0.5 µM, K
d
=.25 µM
[L]=1 µM, [R]=1.25 µM, K
d
=.25 µM
[L]=1 µM, [R]=1.25 µM, K
d
=.5 µM
Affinity = 1 / K
d
B
C
ASlide21
Think-Pair-Share (2 minutes)
Assume the order of response events to an adrenaline spike is:
1st) heart rate increase,
2nd) blood vessel constriction,
3rd) sweating
[ligand]
response
low
high
Which of the following associates the response curves with the physiological response?
Heart = blue,
blood = black,
sweat = green
B) Heart = green,
blood = black,
sweat = blue
C) Heart = black,
blood = blue,
sweat = green
D) All tissues would have the same response curveSlide22
What happens when your
adrenaline rush goes away?
?Slide23
Off-switch (negative threshold
)
Basic response threshold
Maximum response threshold
[Adrenaline]
Fight - Flight response
low
highSlide24
Ligand-receptor interactions are widespread and
have varied roles in organisms.
The immune system
Development
Environmental sensingSlide25
1 Ligand receptor complex
100 - 1000 Ligand receptor complexes
1000 -10,000 Ligand receptor complexes
10,000 -100,000 Ligand receptor complexes
100,000 - 1 million Ligand receptor complexes
How many
ligand
/ receptor complexes are required to elicit a cellular response?Slide26
Summative Assessment
Explain the concept of threshold
Relate changes in dissociation constants to cellular responses
Correlate changing
K
d
values to how they affect the graph
3) Describe the effects that drug A would have on the fight or flight response if drug A:
Lowered the concentration of adrenaline
Blocked the receptor
4)Relate the importance of understanding mathematics to experimentally analyzing cellular responses