Membrane metabolism mediated by Sec14 family members influences Arf GTPase activating protein activity for transport from the trans-Golgi.

Membrane metabolism mediated by Sec14 family members influences Arf GTPase activating protein activity for transport from the trans-Golgi.
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Sec14 家族成员介导的膜代谢影响 Arf GTP 酶激活蛋白活性,以从反式高尔基体转运。

DOI:
10.1073/pnas.0506156102
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发表时间:
2005
影响因子:
11.1
通讯作者:
G. C. Johnston
G. C. Johnston
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tania A. Wong;G. Fairn;P. P. Poon;M. Shmulevitz;C. McMaster;R. A. Singer;G. C. Johnston

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酿酒酵母芽生菌体中含有一组ADP核糖化因子GTP酶激活蛋白(GAP)家族,其Gcs1+AGE2 ArfGAP对为运输小泡从跨高尔基体网络中的运动提供了必要的重叠功能。我们已经产生了一个温度敏感但稳定的Gcs1蛋白版本,它只在跨高尔基体运输时受损,并发现这种减弱的Gcs1-4突变蛋白的有害影响可以通过增加gcs1-4突变基因本身的基因剂量或通过编码磷脂酰肌醇转移蛋白(PITP)的SFH2基因(也称为CSR1)来缓解。在编码酵母PITP蛋白家族创始成员的SEC14基因中没有发现这种影响,尽管已知Gcs1和AGE2 ArfGAP是Sec14介导的跨高尔基体运输活性的下游效应者。Sfh2介导的对Gcs1-4功能不足的抑制依赖于磷脂酶D,而Gcs1-4活性不足可通过增加二酰甘油(DAG)水平来缓解。重组Gcs1蛋白可与某些磷脂结合,但不能与DAG结合。我们的发现支持Gcs1定位的模型,该模型是通过与特定的磷脂结合并在运输囊泡形成时通过DAG介导膜曲率激活ArfGAP活性来实现的。因此,ArfGAP同时受到时间和空间调节,这是由Sfh2介导的脂质环境调节促进的。
The budding yeast Saccharomyces cerevisiae contains a family of Arf (ADP-ribosylation factor) GTPase activating protein (GAP) proteins with the Gcs1 + Age2 ArfGAP pair providing essential overlapping function for the movement of transport vesicles from the trans-Golgi network. We have generated a temperature-sensitive but stable version of the Gcs1 protein that is impaired only for trans-Golgi transport and find that deleterious effects of this enfeebled Gcs1-4 mutant protein are relieved by increased gene dosage of the gcs1-4 mutant gene itself or by the SFH2 gene (also called CSR1), encoding a phosphatidylinositol transfer protein (PITP). This effect was not seen for the SEC14 gene, encoding the founding member of the yeast PITP protein family, even though the Gcs1 and Age2 ArfGAPs are known to be downstream effectors of Sec14-mediated activity for trans-Golgi transport. Sfh2-mediated suppression of inadequate Gcs1-4 function depended on phospholipase D, whereas inadequate Gcs1-4 activity was relieved by increasing levels of diacylglycerol (DAG). Recombinant Gcs1 protein was found to bind certain phospholipids but not DAG. Our findings favor a model of Gcs1 localization through binding to specific phospholipids and activation of ArfGAP activity by DAG-mediated membrane curvature as the transport vesicle is formed. Thus, ArfGAPs are subject to both temporal and spatial regulation that is facilitated by Sfh2-mediated modulation of the lipid environment.
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。
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期刊: MOLECULAR CELL
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发表时间: 2000-08-01
影响因子: 3.3
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