ABSTRACT Phospholipids of cell membranes are asymmetrically arranged. Phosphatidylserine and phosphatidylethanolamine mainly reside in the inner membrane leaflet while phophatidylcholine and sphingomyelin mainly reside in the outer leaflet. Cell activation, injury and apoptosis goes along with a decrease of phospholipid asymmetry and accumulation of phosphatidylserine in the outer membrane leaflet. This accumulation promotes recognition and clearance of the cells by phagocytes as well as the activation of enzymes of the coagulation cascade in the case of platelets. Decrease of phospholipid asymmetry is assumed to result from the activation of a phospholipid scramblase (PLSCR) which enhances bidirectional transbilayer movement of membrane phospholipids. PLSCRs are a family of membrane proteins with a single transmembrane domain and conserved Ca2+ binding region proximal to this domain. Four PLSCRs have been cloned in humans as well as orthologues in the mouse and rat. Human PLSCR1 has several phosphorylation sites and is palmitoylated. It has binding sites for SH3 and WW-domains of other proteins at the N-terminal segment. Binding of Ca2+ produces a conformational change of PLSCR1 which may trigger enhancement of transbilayer movement of membrane phospholipids. This role of PLSCR1 has recently been questioned. In addition, a role of PLSCR1 in cell signalling is indicated by its enrichment in lipid rafts, its tyrosine phosphorylaton upon stimulation of the EGF or IgE receptor, its phosphorylation by c-Abl tyrosine kinase and protein kinase C delta, its enhanced expression by interferons, as well as its targeting to the nucleus in case of absence of palmitoylation. These results suggest roles of PLSCR1 in immune response, cell proliferation, differentiation, and apoptosis.
Buy this Article
|