Ongoing Project
Characterization of the lipid flippase ATP8A2, and its role in neurodegenerative diseases
Lipid flippases are essential membrane proteins widely expressed in cells. These lipid transporters responsible for generating and maintaining membrane lipid asymmetry, a cellular feature essential for a wide range of cellular pathways such as cell signaling, protein trafficking, blood coagulation, and apoptosis. My project seeks to further our understanding of how loss of function mutations in the lipid flippase, ATP8A2 causes severe neurodegenerative disease, and the different mechanisms this protein utilizes to regulate its activity.
Topological model of ATP8A2 and its accessory subunit CDC50A. ATP8A2 consists of 10 transmembrane segments, a nucleotide binding domain (N), a phosphorylation domain (P) and an actuator (A) domain. A number of missense mutations in ATP8A2 which causes a neurodevelopmental disease CAMRQ-4 are shown. CDC50A consists of a glycosylated exoplasmic domain flanked by transmembrane segments.