Aminophospholipid translocase

An ATP-dependent aminophospholipid translocase activity in plasma membranes prevents this occurrence in healthy cells. 

Reviews of the role of aminophospholipid translocase and scramblase (Schlegel et al, 2000) and the consequences of the appearance of phosphatidylserine on the cell surface (Williamson et al, 2001) in apoptosis of thymocytes have been published. The precise relationship between membrane phospholipid asymmetry and apoptosis is currently a topic of considerable interest. 

Chen, C.Y., Ingram, M.F., Rosal, P.H. and Graham, T.R., 1999, Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. J. Cell. Biol, 147 1223-1236. 

Ding, J, Wu, Z, Crider, B.P., Ma, Y., Li, X., Slaughter, C., Gong, L. andXie, X.S., 2000, Identification and functional expression of four isoforms of ATPase II, the putative aminophospholipid translocase. Effect of isoform variation on the ATPase activity and phosphohpid specificity. J. Biol Chem., 275 23378-23386. 

In many eukaryotic plasma membranes, PS resides in the inner leaflet (Schroit and Zwaal, 1991 Zachowski, 1993). This transbilayer distribution of membrane hpids is not a static situation but a result of balance between the inward and outward translocation of phospholipids across the membranes. Recent studies showed that the transbilayer lipid asymmetry is regulated by several lipid transporter proteins, such as aminophospholipid translocase (Daleke and Lyles, 2000), ATP-binding cassette transporter family (van Helvoort et al, 1996 Klein et al, 1999), and phospholipid scramblase (Zhou et al, 1997 Zhao et al, 1998). An increment of intracellular due to cell activation, cell injury, and apoptosis affects the activities of these transporters, resulting in exposure of PS (Koopman et al, 1994 Verhoven et al, 1995) and PE (Emoto et al, 1997) on the cell surface. 

Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enchanced by loss of the aminophospholipid translocase, J. Biol. Chem. 272 26159-26165. 

B13. Bratton, D. L., Fadok, V. A., Richter, D. A., Kailey, J. M., Guthrie, L. A., and Henson, P. M., Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated non-specific flip-flop and is enhanced by loss of aminophospholipid translocase. J. Biol. Chem. 272, 26159-26165 (1997). 

Tilly RHJ, SendenJMG, Comfurius R Bevers EM, Zwaal RFA. Increased aminophospholipid translocase activity in human platelets during secretion. Biochem Biophys Acta 1990 1029 188-190. 

The aminophospholipid translocase is an ATPase II-type enzyme that requires Mg2+ and is activated by phosphatidylserine and to a lesser extent by phosphatidylethanolamine and is sensitive to the sulphydryl group... 

Gomes, E., Jakobsen, M.K., Axelsen, K.B., Geisler, M. and Palmgren, M.G., 2000, Chilling tolerance in Arabidopsis involves ALAI, a member of a new family of aminophospholipid translocases. Plant Cell, 12 2441-2454. 

Herrmann, A., and Devaux, P.F., 1990, Alternation of the aminophospholipid translocase activity during in vivo and artificial aging of human erythrocytes, Biochim. Biophys, Acta 1027 41-46. 

Aminophospholipid translocases. Numerous studies using either short-chain versions of PS, or spin-labeled, or fluorescent analogs of PS and PE established the general... 

ANTIPROTOZOAL EFFECTS Miltefosine is the first orally available therapy for leishmaniasis. It is safe and effective treatment for visceral leishmaniasis and has also shown >95% efficacy against cutaneous leishmaniasis. In Leishmania, the drug may alter ether-lipid metabohsm, ceU signaling, or glycosylphosphatidylinosital anchor biosynthesis. Mutations in a P-type ATPase of the aminophospholipid translocase subfamily apparently decrease drug uptake and thereby confer resistance. 

In the early stages of apoptosis, plasma membrane alterations occur at the cell surface, and PS translocates from the inner side to the outer layer of the plasma membrane. PS and phosphatidylethanolamine are actively confined to the inner cytofacial leaflet of the plasma membrane by the aminophospholipid translocase. This has been identified as a trigger for stimulation of the phagocytosis of apoptotic cells by macrophages, thus preventing secondary necrosis and inflammation of the surrounding tissue. 

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