Sunday September 23, 2012 12:15 - 12:30 @ Rhodes 8 

The lipid flippase TAT-5 inhibits the budding of extracellular vesicles from the surface of C. elegans embryos

Abstract:

Cells release extracellular vesicles (ECVs) that can influence differentiation, modulate the immune response, promote coagulation, and induce metastasis. Many ECVs form by budding outwards from the plasma membrane, but the molecules that regulate budding are unknown. In ECVs, the outer leaflet of the membrane bilayer contains aminophospholipids that are normally sequestered to the inner leaflet of the plasma membrane, suggesting a potential role for lipid asymmetry in ECV budding.

We show that loss of the conserved lipid flippase TAT-5 causes the large-scale shedding of ECVs and disrupts cell adhesion and morphogenesis in C. elegans embryos. ECVs accumulate between cells disrupting the structure of cell-cell contacts. TAT-5 localizes to the plasma membrane and its loss results in phosphatidylethanolamine (PE) exposure on cell surfaces, suggesting that TAT-5 maintains plasma membrane PE asymmetry. Since viruses also bud from the surface of cells, we tested whether viral budding regulators also regulate ECV budding. We show that RAB-11 and endosomal sorting complex required for transport (ESCRT) proteins are enriched at the plasma membrane in tat-5 embryos and are required for ECV production.

TAT-5 provides a molecular link between loss of PE asymmetry and the dynamic budding of vesicles from the plasma membrane, supporting the hypothesis that lipid asymmetry regulates budding. Our results also suggest that viral budding and ECV budding may share common molecular mechanisms.