CtBP1/BARS is an activator of phospholipase D1 necessary for agonist-induced macropinocytosis.

CtBP1/BARS is an activator of phospholipase D1 necessary for agonist-induced macropinocytosis.
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DOI:
10.1038/emboj.2009.78
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发表时间:
2009-05-06
期刊:
影响因子:
11.4
通讯作者:
Nakamura, Shun-ichi
Nakamura, Shun-ichi
中科院分区:
生物学1区
文献类型:
--
作者:
Haga, Yuki;Miwa, Noriko;Jahangeer, Saleem;Okada, Taro;Nakamura, Shun-ichi

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囊泡运输,如巨胞饮是一个动态的过程,需要专门的蛋白质和脂质之间的协调相互作用。最近的一份报告表明,CtBP 1/BARS参与表皮生长因子(EGF)诱导的巨胞饮。在巨胞饮作用期间脂质重构如何被调节的详细机制仍不清楚。在这里,我们表明,CtBP 1/BARS是一个生理激活剂的PLD 1所需的激动剂诱导的巨胞饮。EGF诱导的巨胞饮被1-丁醇特异性阻断,但不被2-丁醇阻断。此外,通过血清或EGF刺激细胞导致CtBP 1/BARS与PLD 1的关联。最后,CtBP 1/BARS激活PLD 1与其他PLD激活剂,包括ADP-核糖基化因子,在体外和完整的细胞系统中表现出协同的方式。目前的研究结果揭示了“裂变蛋白”CtBP 1/BARS如何控制包括巨胞饮在内的囊泡运输事件的分子基础。
Vesicular trafficking such as macropinocytosis is a dynamic process that requires coordinated interactions between specialized proteins and lipids. A recent report suggests the involvement of CtBP1/BARS in epidermal growth factor (EGF)-induced macropinocytosis. Detailed mechanisms as to how lipid remodelling is regulated during macropinocytosis are still undefined. Here, we show that CtBP1/BARS is a physiological activator of PLD1 required in agonist-induced macropinocytosis. EGF-induced macropinocytosis was specifically blocked by 1-butanol but not by 2-butanol. In addition, stimulation of cells by serum or EGF resulted in the association of CtBP1/BARS with PLD1. Finally, CtBP1/BARS activated PLD1 in a synergistic manner with other PLD activators, including ADP-ribosylation factors as demonstrated by in vitro and intact cell systems. The present results shed light on the molecular basis of how the ‘fission protein' CtBP1/BARS controls vesicular trafficking events including macropinocytosis.
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