Phosphatidylinositol 4,5-bisphosphate domain inducers promote phospholipid transverse redistribution in biological membranes
Phosphatidylinositol 4,5-bisphosphate domain inducers promote phospholipid transverse redistribution in biological membranes
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DOI：
10.1021/bi992403l
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发表时间：
2000-05-16
期刊：
影响因子：
2.9
通讯作者：
Sulpice, JC
中科院分区：
文献类型：
--
作者：
Bucki, R;Giraud, F;Sulpice, JC
跨膜磷脂再分布（混乱），导致暴露在细胞表面的磷脂酰丝氨酸，发挥生理作用，诱导血小板促凝血活性和清除损伤或凋亡细胞。扰乱通常归因于细胞内Ca 2+的增加，并由蛋白质（扰乱酶）介导，其活性可由辅因子调节。我们先前报道了磷脂酰肌醇4，5-二磷酸（PIP 2）是Ca 2+诱导的混乱的正调节剂。我们在这里显示，使用来自红细胞膜的由内而外的囊泡，与PIP 2高亲和力相互作用的普列克底物蛋白同源（PH）结构域抑制Ca 2+诱导的混乱，证实了PIP 2的作用。由于Ca 2+与PIP 2相互作用，并促进膜中酸性磷脂侧域的形成，我们研究了PIP 2结构域的形成是否可能参与加扰。精胺、多聚赖氨酸和MARCKS（151-175）肽引起的混乱与它们形成酸性磷脂（包括PIP 2）结构域的报道能力平行。类似地，新霉素，另一种PIP 2相互作用的聚阳离子，诱导混乱。还发现PIP 2抗体诱导乱序，推测是通过类似的机制，因为已知磷脂抗体促进磷脂加帽。总之，Ca 2+不是唯一的诱导混乱，和PIP 2结构域的形成可能在这个过程中发挥关键作用。
Transmembrane phospholipid redistribution (scrambling), leading to exposure of phosphatidylserine on the cell surface, plays a physiological role to induce platelet procoagulant activity and clearance of injured or apoptotic cells. Scrambling is generally attributed to an increase in intracellular Ca2+ and would be mediated by a protein (scramblase), whose activity could be modulated by cofactors. We reported previously that phosphatidylinositol 4,5-bisphosphate (PIP2) is a positive regulator of Ca2+-induced Scrambling, We show here, using inside-out vesicles from erythrocyte membranes, that a pleckstrin homology (PH) domain, which interacts with high affinity with PIP2, inhibited Ca2+-induced scrambling, confirming the role of PIP2. As Ca2+ is known to interact with PIP2 and to promote the formation of lateral domains of acidic phospholipids in membranes, we investigated whether PIP2 domain formation could be involved in scrambling. Spermine, polylysine, and MARCKS (151-175) peptide caused scrambling in parallel to their reported ability to form domains of acidic phospholipids, including PIP2. Similarly, neomycine, another PIP2-interacting polycation, induced scrambling. A PIP2 antibody was also found to induce scrambling, presumably by a similar mechanism, since phospholipid antibodies are known to promote phospholipid capping. In conclusion, Ca2+ is not the sole inducer of scrambling, and formation of PIP2 domains could play a critical role in this process.