Question

You must cite your sources. I am expecting the length of your answer to be between 0.75 -1.5 pages (but there is no strict requirement). You may include figures with citations (not included in length of answer). Describe the basic mechanism of Notch signaling. Include: Discussion of ligand-receptor interaction Proteolysis of the receptor Role of the cytoplasmic tail of the receptor The role of Notch signaling in lateral inhibition in the developing fly eye. Describe the basic mechanism of canonical Wnt signaling. Include: Discussion of ligand-receptor interaction Events that occur prior to ligand-receptor binding Roles/presence of beta catenin in different cellular locations (there are 3 locations) The role of Wnt signaling in dorsal/ventral patterning of the developing neural tube.

Please answer question 1, thanks!

Answer 1

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Notch signalling is an important molecular event which controls many downstream functions. At least 4 type of notch receptors are found on the plasma membrane of mammalian cells. Structurally, these notch receptors span the whole plasma membrane only once. They have a very large extracellular receptor domain and also comprise of a small intracellular domain. The ligand-receptor binding for notch signalling is calcium dependent. This large extracellular domain interacts with another smaller extracellular domain of another notch-receptor of a cell by a calcium-dependent mechanism. As these receptors receive the signals and a cascade of events start.

As the ligand binds to the extracellular domain, it activates the intracellular domain of notch receptor and it undergoes proteolytic cleavage. The cytoplasmic domain of the notch receptor contains lysine residues which are targets for proteolytic cleavage by ubiquitibation. This releases the intracellular smaller domain of notch receptor in the cytoplasm and this released domain moves towards nucleus. This smaller peptide then enters the nucleus and modulates gene expression.

The notch signalling has an important role in lateral inhibition of eye development in fly. Lateral inhibition refers to feedback inhibition of cellular division due to lateral occupancy of one cell to another. Just as contact inhibition prevents further proliferation of cells in all directions, lateral inhibition occurs only bidireactionally. A specific example is failure of development of eye in fruit fly. Molecular explanation behind this fact is that since the notch receptors carry very large cytoplasmic domains, the presence of another cell with cytoplsmic domain in close proximity to it modulates the function of notch signalling in the first cell. A very common effect of this feedback inhibition is failure to proliferate. Due to same reason, fruit flies fail to develop eyes properly owing to faulty notch signalling.