Name: Paulina Cruz de Casas
PI: Prof. Dr. med. Wolfgang Kastenmüller
Institute: Institute of Systems Immunology I
Funding: DFG GRK2581: Metabolism, topology and compartmentalization of membrane-related lipid and signal components in infection
Project: SMPDL3B is a sphingomyelinase located in the outer leaflet of the plasma membrane, which we know is enriched in sphingomyelin, forming part of lipid rafts; it has been suggested that lipid rafts may act as platforms for the clustering of different receptors, such as the TCR, to enhance signaling and cell responses. The physiological substrate and function of this enzyme is largely unknown and the published literature on this enzyme is very limited, but its structural similarity to other sphingomyelinases and its active site suggest sphingomyelinase activity. SMPDL3B is upregulated in effector and memory CD8+ T cells when compared to naive CD8+ T cells, where it is not expressed. Since this enzyme seems to regulate the migration of other cell types and due to its particular location in the plasma membrane within lipid rafts, we hypothesize that SMPDL3B regulates the TCR-mediated signaling responsiveness and migratory capacity via changes in membrane fluidity.