Abstract by Colten McEwan
Chemistry and Biochemistry
Identifying LRBA as a Novel ATG9A Trafficking Regulator
Autophagy is a cellular recycling process that leads to disease when it is dysregulated. How defective autophagy causes disease is unclear. This is partly because autophagy mechanisms are still uncertain. One uncertain regulator of autophagy is the multi-pass transmembrane protein ATG9A. It is an essential autophagy protein that has few known interactors. To discover interactors, our lab used a biotin labeling technique called BioID and developed a bank of possible ATG9A interacting preoteins. Foremost of these proteins is the vesicle trafficking regulator Lipopolysaccharide-Responsive Beige-Like Anchor Protein (LRBA). Human mutations in LRBA cause a rare immune disorder that leads to dysregulated autophagy for unknown reasons. We validate LRBA as an ATG9A interactor and measure how LRBA deletion affects autophagy. Furthermore, we demonstrate that LRBA is an ATG9A trafficking regulator. We hypothesize that LRBA disease is caused by dysregulated ATG9A trafficking and propose an experimental model to prove our hypothesis.