The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells.
The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells.
复制标题
Rab8 GTPase 选择性调节极化 Madin-Darby 犬肾细胞中 AP-1B 依赖性基底外侧转运。
DOI：
10.1083/jcb.200307046
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发表时间：
2003-10-27
影响因子：
7.8
通讯作者：
Mellman, I
中科院分区：
文献类型：
--
作者：
Ang, AL;Fölsch, H;Koivisto, UM;Pypaert, M;Mellman, I
AP - 1B网格蛋白衔接蛋白复合物在上皮细胞基底外侧表面许多膜蛋白的识别和细胞内运输中起关键作用。然而，对于与AP - 1B协同作用的其他成分知之甚少。我们发现Rab8 GTP酶就是这样一种成分。组成型激活的GTP水解突变体的表达选择性地抑制了新合成膜蛋白的基底外侧（而非顶端）运输。此外，这种影响仅限于依赖AP - 1B的基底外侧货物；含有不与AP - 1B相互作用的双亮氨酸靶向基序的蛋白质的基底外侧运输尽管突变体Rab8过表达，但仍正常靶向。对于Rho GTP酶Cdc42的显性负性等位基因也获得了类似的结果，该基因先前与基底外侧运输有关，但现在显示对AP - 1B途径具有选择性。Rab8 - GFP与AP - 1B复合物以及密切相关但普遍表达的AP - 1A复合物一起定位于反式高尔基体网络（TGN） - 再循环内体的膜上。然而，活性Rab8的表达导致AP - 1B复合物的选择性解离，反映了Rab8对依赖AP - 1B的运输的特异性。
The AP-1B clathrin adaptor complex plays a key role in the recognition and intracellular transport of many membrane proteins destined for the basolateral surface of epithelial cells. However, little is known about other components that act in conjunction with AP-1B. We found that the Rab8 GTPase is one such component. Expression of a constitutively activated GTP hydrolysis mutant selectively inhibited basolateral (but not apical) transport of newly synthesized membrane proteins. Moreover, the effects were limited to AP-1B–dependent basolateral cargo; basolateral transport of proteins containing dileucine targeting motifs that do not interact with AP-1B were targeted normally despite overexpression of mutant Rab8. Similar results were obtained for a dominant-negative allele of the Rho GTPase Cdc42, previously implicated in basolateral transport but now shown to be selective for the AP-1B pathway. Rab8-GFP was localized to membranes in the TGN-recycling endosome, together with AP-1B complexes and the closely related but ubiquitously expressed AP-1A complex. However, expression of active Rab8 caused a selective dissociation of AP-1B complexes, reflecting the specificity of Rab8 for AP-1B–dependent transport.
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影响因子：
64.5
作者：
Fölsch, H;Ohno, H;Mellman, I
通讯作者：
Mellman, I
影响因子：
56.9
作者：
Carroll, KS;Hanna, J;Pfeffer, SR
通讯作者：
Pfeffer, SR
影响因子：
4.5
作者：
Cohen, D;Müsch, A;Rodriguez-Boulan, E
通讯作者：
Rodriguez-Boulan, E
影响因子：
4.8
作者：
Erickson, JW;Zhang, CJ;Cerione, RA
通讯作者：
Cerione, RA
影响因子：
7.8
作者：
Hirst, J;Lui, W W;Bright, N A;Totty, N;Seaman, M N;Robinson, M S
通讯作者：
Robinson, M S