Student Metropolitan State University of Denver Denver, Colorado, United States
John Manalastas (Metropolitan State University of Denver)| Elizabeth Spear (Metropolitan State University of Denver)| Megan Filbin (Metropolitan State University of Denver)
Mutations in the deleted colorectal cancer (DCC) protein, a transmembrane protein receptor residing at the growth cones of neurons, result in mirror movement disorders. DCC coordinates axonal protein synthesis in response to netrin-1 signaling. Mutations that prevent netrin-1 signaling lead to stalled translation machinery at DCC’s cytoplasmic tail (C-tail), ultimately preventing proper neuron networking during the spinal cord development, and leading to involuntary mirrored movements to the other side of the body. Yet, the way in which DCC regulates protein synthesis is unknown. Using recombinant protein expression of DCC’s C-tail and in vitro luciferase translation reporter assays, we show that DCC regulates translation at the initiation step. To further define DCC’s mechanism, we used RNA pull-down and Western blot experiments with and without purified DCC C-tail to determine how DCC affects the initiation process. These experiments, combined with mutational analysis, lead to a better understanding of how DCC regulates the translation machinery. Our focus may lead to better understand the growth process of neuronal axons relating to mirror movement disorders and create a model for the DCC regulation.