Differential Effects of Depletion of ARL1 and ARFRP1 on Membrane Trafficking between the trans-Golgi Network and Endosomes
Differential Effects of Depletion of ARL1 and ARFRP1 on Membrane Trafficking between the trans-Golgi Network and Endosomes
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DOI：
10.1074/jbc.m900847200
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发表时间：
2009-04-17
影响因子：
4.8
通讯作者：
Nakayama, Kazuhisa
中科院分区：
文献类型：
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作者：
Nishimoto-Morita, Kirika;Shin, Hye-Won;Nakayama, Kazuhisa
ARFRP1和ARL1都是类似arf的小gtpase，分别是酵母Arl3p和Arl1p的哺乳动物同源物。在酵母中，靶向反式高尔基网络（TGN）膜的Arl3p激活了Arl1p，而被激活的Arl1p又招募了一个含有GRIP结构域的蛋白；这个复合物调节到TGN的逆行运输和从TGN的顺行运输。在本研究中，我们利用RNA干扰介导的ARFRP1和ARL1的敲低，研究了Arl3p-Arl1p-GRIP的同源基因是否在哺乳动物细胞中具有类似的功能。然而，我们意外地发现了ARL1和ARFRP1的不同作用。具体来说，ARL1和ARFRP1分别调节志贺毒素向TGN的逆行运输和VSVG从TGN的逆行运输。此外，我们已经获得证据表明含有Vti1a、syntaxin 6和syntaxin 16的SNARE复合物参与了志贺毒素在ARL1下游的转运。
ARFRP1 and ARL1, which are both ARF-like small GTPases, are mammalian orthologs of yeast Arl3p and Arl1p, respectively. In yeast, Arl3p targeted to trans-Golgi network (TGN) membranes activates Arl1p, and the activated Arl1p in turn recruits a GRIP domain-containing protein; this complex regulates retrograde transport to the TGN and anterograde transport from the TGN. In the present study, using RNA interference-mediated knockdown of ARFRP1 and ARL1, we have examined whether the orthologs of Arl3p-Arl1p-GRIP story serve similar functions in mammalian cells. However, we have unexpectedly found differential roles of ARL1 and ARFRP1. Specifically, ARL1 and ARFRP1 regulate retrograde transport of Shiga toxin to the TGN and anterograde transport of VSVG from the TGN, respectively. Furthermore, we have obtained evidence suggesting that a SNARE complex containing Vti1a, syntaxin 6, and syntaxin 16 is involved in Shiga toxin transport downstream of ARL1.