Question

4. There are a variety of receptors and second messenger systems in cells that in many cases exhibit cross-talk with each other (the activation of one can influence the behavior of another). Given this fact understanding how ligand activated receptors works is not as easy as presented in your book or in class.

a. There are a number of different ligands that interact with their respective receptors. How do receptors for testosterone, ferro transferrin and Fibroblast Growth Factor differ from each other with respect to the location and function of their receptors?

b. The proper operation of our LDL system is critical to our LDL/HDL ratio which is a typical component of most blood tests done when you are having a physical. The ideal ratio is 3.5 to 1. In select cases, however, LDL is in very high concentrations in the blood resulting in familiar hypercholesterolemia (FH).

            i. CHALLENGE: There are a number of different genetic defects that can cause FH. You are working with a cell line from a patient with FH and need to determine if the LDL defect is due to the low number of LDL receptors present in the membrane, its ligand binding affinity or mutations (amino acid substitutions) in the NPXY sequence. How might you accomplish this task?

c. Many cancers are characterized by defects in the RTK system. What are some of these defects and why aren't defects in the LDL or ferro transferrin systems implicated in cancer?

d. The visual transduction system was a challenging molecular cascade to fully elucidate. One of the biggest challenges was that light caused a hyperpolarization of the transmembrane electrical potential whereas for a typical neuron such as a motor neuron a stimulus causes a depolarization with an accompanying action potential. Explain why light causes this hyperpolarization in the rod photoreceptor.

e. The visual transduction system is a marvelous system for several reasons not the least of which includes its ability to adapt to different levels of ambient light. How is this accomplished?

Answer 1

Answer Tay The difference between the 3 types of receptor rovided in the question are as follows" - Testosterone ferro Fibroblast receptor - Transferrin I Growth receptor Feector I seeeptor The receptor. - is located. The receptor in weated ody in i on the cell l on cell . ceftoplasm e and i surface, surface.. ugand binding It is a nuclear receptor, and norma le ca franslocates лие оши On bendera the ligando in cytosol and then the receptor es trans located to the nucleus and for then binds to a specific sequence on DNA by try into the Its receptor After binding binding of l belongs to to its recepton, the family, 1. the fe-transferrin of RTU louses the complex is. . (Receptor rapidly internali- i ra dissociation of heat shock I zed by invaginar Minase). proteins from tion of clathrin ! Binding l of the coated pits with the receptor formation of Ugand al to the endocytic vessicles. ! reeeptor After detaching causes the re-transferrin dimeni zation complex, the land auto- receptor is Iphosphor recycled again trglation to the cell surface (sonic jof cyto forming dimers, domain and then cross- Iphosphorylate each other on Tyrosine Iresidues i hun c- terminal domain. this may cause o activation of other signalling molecules. to affeet the gene expression. I Such specific sequences are called Hormone response element THRE).

-- wall many cancers must be associated with the mal functionina thoning of the Role growth receptors. eg- Mutations in the EGFR receptor. may cause change in the receptor in such a way that it becomes constitutively. activated and can cause continuous signallung even without the presence of ligand. The RTK can also a stimulate the Ras path way that is responsible for all division control a leading to loss of: control ein cell division The Rih can overstimulate the P1-3/Akt signalling pathway and unrolled in the inhibition of apoptosis and cell survival leading to cancer. d No, defects in LDL or ferrotransferin system, does not implicated in cancer because they are not the involved ooth differe cell division or een death pathway. They mainly sis bu mainly the .. roliferation pathway tollow secep for medialed ein o o and get stored in the caneer is caused by mainly th growth and proliferation defect. the Rod photoreceptor rom wh . cells, Rhodopsin absorps the light. ... Leading to change in conformation i cis retinal to all trans-retinal This activates Trans du cin Cactine as G-protein), which activate AGMP phosphodiesterase (por (PDE)

that brealls CGMP to 5-GMP. Reduction i in comp allows con channel to close preventing the influx of positive ion expolar ming the cell and stopping the release of neurotransmitless. the a Hyperpolarizing In light Rhodopsin flight a Alu-trans retinal ADID lleis - Retinal Transducin (G-protein) I activate CGMP Phosphodiesterase " i PDE) 5-GMP (GMP - con channel to close due to low comp. Membrane hyperpolarization occurs release rotramither Neurol Stopped.

The question does not mention the number of question to be answered, so i am providing the answers for the first 4 parts of the question.The answers are explained in the pictures above.