BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: Its localization to recycling endosomes and implication in the endosome integrity
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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DOI：
10.1091/mbc.e04-05-0388
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发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Nakayama, K
中科院分区：
文献类型：
--
作者：
Shin, HW;Morinaga, N;Nakayama, K
adp核糖基化因子（ARF）家族的小gtpase通过调节被包膜囊泡的形成在膜运输中起关键作用，鸟嘌呤核苷酸交换对于ARF功能至关重要。Brefeldin A通过抑制arf上的鸟嘌呤核苷酸交换来阻断arf触发的外壳组装，并导致高尔基复合体的解体和内体膜的管化。BIG2是brefeldin a抑制ARF gtpase的鸟嘌呤核苷酸交换因子之一，主要与反式高尔基网络有关。在本研究中，我们发现了BIG2的另一个种群与循环核内体相关，并发现一个催化失活的BIG2突变体E738K的表达选择性地诱导了膜小管的产生。我们还发现，在体内，BIG2对I类ARF （ARF1和ARF3）具有交换活性，并且任何一种ARF的失活都会加剧BIG2（E738K）诱导的内体膜管化。这些观察结果共同表明，BIG2通过激活I类arf参与了再循环核内体的结构完整性。
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.