Functional Analyses of the Kek5 Intracellular SLiM, CO1, in Drosophila and Disease Implications in Humans

Heffernan, Kelly

Student Work

Functional Analyses of the Kek5 Intracellular SLiM, CO1, in Drosophila and Disease Implications in Humans

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Controlled and orchestrated cell signaling pathways are paramount for proper cellular and organismal development and function. Bone Morphogenetic Protein (BMP) signaling represents one of the most highly conserved pathways whose dysregulation in humans leads to skeletal, cardiovascular, and metabolic diseases, as well as numerous types of cancer. Model organisms, like Drosophila, provide a way to characterize the function of such conserved cell signaling proteins and pathways in vivo. Kekkon5 (Kek5) is a transmembrane regulator of BMP signaling in Drosophila. Strikingly, Kek5 was recently shown to putatively contain an intracellular motif found in the human Deleted in Colorectal Cancer (DCC) receptor, which regulates DCC activity. In this MQP I focused on determining if this short linear motif (SliM) functions similarly to regulate Kek5’s activity. Specifically, the GAL4/UAS system was used in transgenic Drosophila to compare the function of wild type Kek5 and a variant lacking this SLiM, Kek5ΔCO1, at the organismal and cellular levels. Together, these results indicate that, as in DCC, the CO1 SLiM is indeed critical for regulating Kek5 activity and provides a path forward for future studies. Developing treatments for people who have metabolic, cardiovascular and other diseases from disrupted signaling pathways, including BMP, will ultimately require a detailed understanding of the function of these pathways and their dysregulation in patients.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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