Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast.
Activity of specific lipid-regulated ADP ribosylation factor-GTPase-activating proteins is required for Sec14p-dependent Golgi secretory function in yeast.
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酵母中 Sec14p 依赖性高尔基体分泌功能需要特定脂质调节 ADP 核糖基化因子 - GTP 酶激活蛋白的活性。
DOI：
10.1091/mbc.01-11-0563
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发表时间：
2002
影响因子：
3.3
通讯作者：
Bankaitis,VytasA
中科院分区：
文献类型：
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作者：
Yanagisawa,LoraL;Marchena,Jennifer;Xie,Zhigang;Li,Xinmin;Poon,PakP;Singer,RichardA;Johnston,GeraldC;Randazzo,PaulA;Bankaitis,VytasA
酵母磷脂酰肌醇转移蛋白（Sec14p）协调脂质代谢与蛋白质转运事件。控制磷脂酰胆碱或磷酸肌醇代谢的七个基因中的任何一个发生突变，都会绕过对高尔基体功能的必要Sec14p要求。除了这些“绕过Sec14p”突变外，独立于Sec14p的高尔基体功能还需要磷脂酶D （PLD）活性。介导sec14p依赖性高尔基体功能的脂质特性，以及响应sec14p介导的脂质代谢调节的蛋白的特性仍然难以捉摸。我们现在报告的遗传证据表明，两种ARF-GTPase激活蛋白（ARFGAPs） Gcs1p和Age2p可能代表这些脂质响应元件，并且Gcs1p/Age2p在Sec14p依赖和Sec14p独立的酵母高尔基功能途径中作用于Sec14p和PLD的下游。为了支持这一观点，生化数据表明Gcs1p和Age2p ARFGAP活性都受到涉及Sec14p通路功能调节的脂质的调节。这些结果表明，ARFGAPs是通过Sec14p途径调节高尔基体功能所需的刺激因子，并且Sec14p介导的脂质代谢调节与参与控制ARF周期的蛋白质活性相结合。
Yeast phosphatidylinositol transfer protein (Sec14p) coordinates lipid metabolism with protein trafficking events. This essential Sec14p requirement for Golgi function is bypassed by mutations in any one of seven genes that control phosphatidylcholine or phosphoinositide metabolism. In addition to these ‘bypass Sec14p’mutations, Sec14p-independent Golgi function requires phospholipase D (PLD) activity. The identities of lipids that mediate Sec14p-dependent Golgi function, and the identity of the proteins that respond to Sec14p-mediated regulation of lipid metabolism, remain elusive. We now report genetic evidence to suggest that two ARF-GTPase activating proteins (ARFGAPs), Gcs1p and Age2p, may represent these lipid responsive elements, and that Gcs1p/Age2p act downstream of Sec14p and PLD in both Sec14p-dependent and Sec14p-independent pathways for yeast Golgi function. In support, biochemical data indicate that Gcs1p and Age2p ARFGAP activities are both modulated by lipids implicated in regulation of Sec14p pathway function. These results suggest ARFGAPs are stimulatory factors required for regulation of Golgi function by the Sec14p pathway, and that Sec14p-mediated regulation of lipid metabolism interfaces with the activity of proteins involved in control of the ARF cycle.