Transcript No Slide Title

Previously in
Cell Bio
Previously
A) Fluid Mosaic Model
B) Cell Parts: Components
and Organelles
C) Introduction to first case study
Graves’ disease/ hyperthyroidism
Today
Signaling its roles in
Graves’ disease
HowThyroid
are they all
coordinated?
activators
Our Case Study  Thyroid stimulation:
Extracellular signaling and the receptors that mediate it
‘Activating’ Signals:
• Hypothalmus:
Thyrotropin releasing hormone (TRH)
• Pituitary Gland
Thyroid stimulating hormone (TSH)
• Thyroid
T4 (thyroxine)
T3 (triiodothyronine)
Types of Extracellular Signaling
Up close Signaling
•Direct contact
PM receptors
Gap junctions
Secreted ECM
•Autocrine
Through space
•Paracrine
•Endocrine
•Synaptic
types
Normal thyroid function
What types in thyroid regulation?
Endocrine signaling:
(Intracellular receptor
for T4)
Endocrine signaling
PM receptor
Negative feedback loop:
What is it and
why is it important?
BindingSymptoms
vs. Effector
Specificity
in Graves’ Disease
Increase in circulating thyroid hormone causes:
• Increase in secretion by sweat glands
• Increase in rate and force of heart contractions
• Decrease in muscle strength
How can this happen?
Binding vs. effector specificity 2
How can thyroid hormone cause different
responses in different parts of the body?
Ligand needs to bind with receptor
Different cells make different receptors
Same receptor/ligand complex may trigger different
response in a different cell type
Differences between binding specificity
and effector specificity
(Receptors and Ligands? What are they?)
Receptor characteristics
Characteristics of a receptor:
What does it need to have to do its job?
Ribbon diagram of Thyroid hormone
bound to Thyroid hormone receptor
Diagram of isoproterenol bound
to B2 adrengergic receptor
(Fig20-1 Molecular Cell Biology)
Types
Types of Receptors
G-protein linked receptors
(G protein coupled receptors/GPCR)
Ion Channel receptors
Enzyme linked receptors
(Receptor S/T kinases, Receptor Y kinases
Receptor guanylyl cyclases, Protein Y
phosphatases, Y-kinase associated receptors
H-kinase associated receptors)
Intracellular receptors
What’s different in a Grave’s disease patient?
(hyperthyroidism=increased thyroid function)
What happens in Graves’?
Patients have increased T3 and T4 in bloodstream
What might make a thyroid put in overtime?
HYPOTHESES?
Hypothesis : Thyroid being over-stimulated
Normal stimulation results from TSH/receptor
interaction
How does the thyroid know to react?
How does a receptor provide specificity
Hypothesis: Mutation in signaling within cell leading
increase in thyroid hormone production
Normal activation is the result of signal transduction
second messenger cascade
How does signal transduction work?
What could have gone wrong?
Testing the hypotheses
IF hypothesis is true then what is expected?
What data would suggest the hypothesis
needs to be revised?
Tonight: Research Symposium
Tomorrow: 2pm Dr Mimms seminar
Next week: Lecture: How ‘normal’ signals get in
Lab: Analysis of complementation
How much mating is ‘normal’
(‘productive’ response to signal)