Date of Award

Spring 2019

Degree Name

Bachelor of Science

Major

Biochemistry

First Advisor

Robert J. Fleming

Second Advisor

Hebe M. Guardiola-Diaz

Third Advisor

Susan M. Bush

Abstract

The Notch signaling pathway is a highly conserved cell-to-cell signaling system that is present in eukaryotic animals. This pathway plays a significant role during animal development. The Notch gene codes for a protein that functions as a receptor belonging to the single-pass transmembrane protein group. The Notch receptors can interact with ligands that are also single-pass transmembrane proteins of the Delta/Serrate/Lag-2 (DSL) family of ligands. The regulation of the Notch signaling pathway can be controlled through different types of interactions with ligands such as cis-inhibition and trans-activation. The trans-activation interaction occurs when the receptor and ligand proteins, present in neighboring cells, interact. Ligand-receptor interactions can also take place within the cell and on the cell surface, and the cis-interactions can reduce or inhibit the ability of a cell to receive an activating signal from neighboring cells. In activation of Notch, ligands are trafficked through endocytosis and are often regulated by ubiquitin ligase. While it was found that Serrate, a ligand for Notch, is relevant for Notch activity, the importance of the specific localization of Serrate is much less well defined. We postulate that in order to successfully activate Notch, Serrate must be located on the cell surface, however, our data suggest that there may be other properties beyond Serrate localization on the cell surface that dictate the activation of Notch. To test this, we analyzed the different locations of Serrate in cells expressing specific constructs, previously made in Fleming laboratory, with different amino acid lengths in the Juxtamembrane domain, a key component in the structure of Serrate for successful activation. The mechanisms of Notch activation by ligand endocytosis models such as the ligand-recycling model or classical endocytosis model can be the explanation for why Serrate is located on the cell surface while being unable to activate Notch.

Comments

Senior thesis completed at Trinity College, Hartford, CT for the degree of Bachelor of Science in Biochemistry.

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