Unraveling the mysteries of phospholipid scrambling

Plasma membrane phospholipid asymmetry is maintained by an aminophospholipi d translocase that transports phosphatidylserine (PS) and phosphatidylethan olamine (PE) from outer to inner membrane leaflet. Cell activation or injur y leads to redistribution of all major lipid classes within the plasma memb rane, resulting in surface exposure of PS and PE. Cell surface-exposed PS c an serve as receptor sites for coagulation enzyme complexes, and contribute s to cell clearance by the reticuloendothelial system. The mechanism(s) by which this PL "scrambling" occurs is poorly understood. A protein called ph ospholipid scramblase (PLSCR1) has been cloned that exhibits Ca2+-activated PL scrambling activity in vitro, PLSCR1 belongs to a new family of protein s with no apparent homology to other known proteins. PLSCR1 is palmitoylate d and contains a potential protein kinase C phosphorylation site. It furthe r contains multiple PxxP and PPxY motifs, representing potential binding mo tifs for SH3 and WW domains implicated in mediating protein-protein interac tions. Although at least two proteins have been shown to associate with PLS CR1, the functional significance of such interaction remains to be elucidat ed. Evidence that PLSCR1 may serve functions other than its proposed activi ty as PL scramblase is also presented.