Transbilayer Phospholipid Movements in ABCA1-Deficient Cells

• DOI: 10.1371/journal.pone.0000729
• Publication Date: 2007-08-15T21:24:13Z
• Authors: Patrick Williamson; Margaret S. Halleck; Jonathan Malowitz; Susan Ng; Xiaoxuan Fan; Stephen Krahling; Alan T. Remaley; Robert A. Schlegel
• Keywords: Tangier disease; Knockout mouse; Phospholipid scramblase; Wild type

Tangier disease is an inherited disorder that results in a deficiency circulating levels of HDL. Although the known to be caused by mutations ABCA1 gene, mechanism which lesions ATPase effect this outcome not known. The inability knockout mice (ABCA1−/−) load cholesterol and phospholipids onto apoA1 led proposal mediates transbilayer externalization phospholipids, activity integral only formation HDL particles but also another, distinct process: recognition clearance apoptotic cells macrophages. Expression phosphatidylserine (PS) on surface both macrophages their targets required for efficient engulfment cells, it has been proposed PS cell types. To determine whether responsible any catalytic activities control phospholipid movements, these were measured from ABCA1−/− individuals as well ABCA1-expressing HeLa cells. Phospholipid movements either normal or lymphocytes inhibited when wildtype immortalized vs compared. Exposure thymocytes, thymocytes elicited peritoneal B individuals, annexin V binding, was unchanged. No evidence found ABCA1-stimulated active export, spontaneous movement outer leaflet presence absence unaffected ABCA1. Normal identical ability serve phagocytes, respectively, assays. support suggestion involved transport macrophage annexins I II, enhance phagocytosis These show do measurably reduce rate engulfing target, thus discounting catalysis facilitates loading apoA1.