Previously in Cell Bio Previously A Fluid Mosaic

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

How. Thyroid 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 T 4 (thyroxine) T 3 (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 T 4) Endocrine signaling PM receptor Negative feedback loop: What is it and why is it important?

Binding vs. Effector Specificity Symptoms 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 B 2 adrengergic receptor (Fig 20 -1 Molecular Cell Biology)

Types of Receptors

What’s different in a Grave’s disease patient? (hyperthyroidism=increased thyroid function) What happens in Graves’? Patients have increased T 3 and T 4 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– Gallery 7=9 pm Next week: How ‘normal’ signals get in Lab: Analysis of complementation How long does response to signal ‘normally’ last