High content screening to explore human TMEM16C activators

초록

Lipid scrambling is a rapid process that dissipates the asymmetrical distribution of phospholipids in the plasma membrane. It is involved in various physiological functions such as blood coagulation and apoptosis. Many TMEM16 members are recognized as Ca2+ -activated phospholipid scramblases, which transport phospholipids between the two leaflets of the plasma membrane nonspecifically and bidirectionally; among these, TMEM16C is abundant in the brain, especially in neuronal cells. In previous study, we in-vestigated the scrambling activity of three human TMEM16C isoforms. Among three isoforms, membrane lo-calized TMEM16C isoforms 1 and 3 could transport phos-phatidylserine to the outer leaflet. After generating human TMEM16C overexpressing cell-lines, we screened the new modulators for TMEM16C protein by using high content screening. We are currently testing whether these effects were observed only in TMEM16C protein or other TMEM16 family members, TMEM16A and TMEM16F.