Arfaptin 1与ADP-核糖基化因子形成复合物并抑制磷脂酶D。

Arfaptin 1 forms a complex with ADP-ribosylation factor and inhibits phospholipase D.

作者信息

Williger B T, Provost J J, Ho W T, Milstine J, Exton J H

机构信息

Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0295, USA.

出版信息

FEBS Lett. 1999 Jul 2;454(1-2):85-9. doi: 10.1016/s0014-5793(99)00771-1.

DOI:10.1016/s0014-5793(99)00771-1

PMID:10413101

Abstract

ADP-ribosylation factors (ARFs) regulate coatomer assembly on the Golgi as well as recruitment of clathrin adapter proteins and are therefore involved in vesicle budding from the Golgi and vesicular transport. They are also regulators of phospholipase D (PLD) activity. Arfaptin 1 is an ARF binding protein that inhibits PLD activation, vesicular trafficking and secretion. In the present report, we show that arfaptin 1 interacts with 'high speed' membranes independently of ARF. However, addition of myristoylated ARF3 (myrARF3) increases the association of arfaptin 1 with the membranes, suggesting that arfaptin 1 and ARF form a complex on the Golgi. Utilizing several deletion mutants of arfaptin 1 it is shown that the association of arfaptin 1 with myrARF3 is mediated via two binding sites on arfaptin 1. These two domains are needed for arfaptin 1 inhibition of PLD activation by myrARF3 in vitro.

摘要

ADP核糖基化因子（ARFs）调节高尔基体上的包被蛋白组装以及网格蛋白衔接蛋白的募集，因此参与从高尔基体出芽的囊泡形成和囊泡运输。它们也是磷脂酶D（PLD）活性的调节因子。Arfaptin 1是一种ARF结合蛋白，可抑制PLD激活、囊泡运输和分泌。在本报告中，我们表明arfaptin 1与“高速”膜相互作用，且不依赖于ARF。然而，添加豆蔻酰化的ARF3（myrARF3）会增加arfaptin 1与膜的结合，这表明arfaptin 1和ARF在高尔基体上形成复合物。利用arfaptin 1的几个缺失突变体表明，arfaptin 1与myrARF3的结合是通过arfaptin 1上的两个结合位点介导的。这两个结构域是arfaptin 1在体外抑制myrARF3激活PLD所必需的。