Transbilayer asymmetry of phospholipids in the plasma membrane regulates exocytotic release in mast cells
Transbilayer asymmetry of phospholipids in the plasma membrane regulates exocytotic release in mast cells
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DOI：
10.1021/bi016022v
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发表时间：
2002-06-25
期刊：
影响因子：
2.9
通讯作者：
Hirashima, N
中科院分区：
文献类型：
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作者：
Kato, N;Nakanishi, M;Hirashima, N
为了研究质膜磷脂的不对称分布在胞吐作用中的作用，我们检查了脂质的这种不对称分布的破坏对肥大细胞（RBL-2H3）胞吐释放的影响。脂质扰乱酶由二价阳离子激活并催化磷脂的跨双层运动，在肥大细胞中过度表达。外源脂质扰乱酶在质膜和细胞质中表达。二价阳离子激活扰乱酶破坏了质膜中磷脂的不对称分布。在用野生型乱序酶转染的细胞中，由钙离子载体和佛波酯诱导的胞吐释放被显着抑制。观察到这种抑制的时间滞后约5分钟。此外，当脂质的不对称分布在诱导胞吐作用之前被破坏时，胞吐释放的抑制从一开始就很明显，没有滞后。这些结果表明质膜中磷脂的不对称分布在分泌颗粒与质膜之间的融合中起着重要作用。这一发现还表明，磷脂的跨双层不对称性调节胞吐作用，并为质膜中脂质不对称性的重要性提供了新的见解。
To investigate the role of the asymmetric distribution of phospholipids of the plasma membrane in exocytosis, we examined the effects of disruption of this asymmetrical distribution of lipids on exocytotic release from mast cells (RBL-2H3). Lipid scramblase, which is activated by divalent cations and catalyzes the transbilayer movement of phospholipids, was overexpressed in mast cells. Exogenous lipid scramblase was expressed in the plasma membrane and the cytoplasm. Activation of scramblase by divalent cations disrupted the asymmetrical distribution of phospholipids in the plasma membrane. Exocytotic release induced by calcium ionophore and phorbol ester was significantly inhibited in the cells transfected with wild-type scramblase. This inhibition was observed with time lag of about 5 min. Furthermore, when the asymmetric distribution of lipids was disrupted before induction of exocytosis, the inhibition of exocytotic release was obvious from the beginning without the lag. These results suggest that the asymmetric distribution of phospholipids in the plasma membrane plays an essential role in fusion between secretory granules and the plasma membrane. This finding also demonstrates that the transbilayer asymmetry of phospholipids regulates exocytosis and gives a new insight into the significance of lipid asymmetry in the plasma membrane.