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首页> 外文期刊>Molecular biology of the cell >BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its localization to recycling endosomes and implication in the endosome integrity
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BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its localization to recycling endosomes and implication in the endosome integrity

机译：BIG2，ADP-核糖基化因子的鸟嘌呤核苷酸交换因子：其定位于回收内体和内体完整性的暗示

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摘要

Small GTPases of the ADP-ribosylation factor (ARF) family play a key role in membrane trafficking by regulating coated vesicle formation, and guanine nucleotide exchange is essential for the ARF function. Brefeldin A blocks the ARF-triggered coat assembly by inhibiting the guanine nucleotide exchange on ARFs and causes disintegration of the Golgi complex and tubulation of endosomal membranes. BIG2 is one of brefeldin A-inhibited guanine nucleotide exchange factors for the ARF GTPases and is associated mainly with the trans-Golgi network. In the present study, we have revealed that another population of BIG2 is associated with the recycling endosome and found that expression of a catalytically inactive BIG2 mutant, E738K, selectively induces membrane tubules from this compartment. We also have shown that BIG2 has an exchange activity toward class I ARFs (ARF1 and ARF3) in vivo and inactivation of either ARF exaggerates the BIG2(E738K)-induced tubulation of endosomal membranes. These observations together indicate that BIG2 is implicated in the structural integrity of the recycling endosome through activating class I ARFs.
机译：ADP-核糖基化因子（ARF）家族的小GTPases通过调节包被的囊泡形成在膜运输中起关键作用，而鸟嘌呤核苷酸交换对于ARF功能至关重要。布雷菲德菌素A通过抑制ARF上的鸟嘌呤核苷酸交换来阻断ARF触发的外皮装配，并导致高尔基复合体解体和内膜膜小管化。 BIG2是布雷菲德菌素A抑制ARF GTPases的鸟嘌呤核苷酸交换因子之一，并且主要与反高尔基网络有关。在本研究中，我们揭示了另一群BIG2与回收内体有关，并发现催化失活的BIG2突变体E738K的表达选择性地诱导了该小室的膜小管。我们还显示，BIG2在体内具有对I类ARF（ARF1和ARF3）的交换活性，并且任一ARF的失活都夸大了BIG2（E738K）诱导的内体膜微管的形成。这些观察结果共同表明，BIG2通过激活I类ARF参与了回收内体的结构完整性。

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