Dependence on different Rab GTPases for the trafficking of CXCR4 and CCR5 homo or heterodimers between the endoplasmic reticulum and plasma membrane in Jurkat cells
Dependence on different Rab GTPases for the trafficking of CXCR4 and CCR5 homo or heterodimers between the endoplasmic reticulum and plasma membrane in Jurkat cells
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DOI：
10.1016/j.cellsig.2011.06.008
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发表时间：
2011-11-01
影响因子：
4.8
通讯作者：
Dupre, Denis J.
中科院分区：
文献类型：
--
作者：
Charette, Nicholle;Holland, Patrick;Dupre, Denis J.
关于G蛋白偶联受体在激动剂刺激后的运输和内化，我们已经知道很多。然而，关于受体从内质网合成到质膜的向外运输，或者运输在受体信号传导复合物的组装中可能发挥的作用，对于随后的信号传导事件的靶向，特异性和快速性很重要，了解得很少。到目前为止，很少有人了解受体异源寡聚体以外的事实，即它们的组装是在生物合成后迅速完成。在我们的研究中，我们使用双分子荧光互补选择性地跟随受体二聚体在Jurkat细胞中表达时，以澄清这些受体随后到达质膜的运输路线以及对信号转导的影响。CXCR 4和CCR 5，以前显示形成同源和异源寡聚体，被用作我们的模型，以了解运输的特异性沿着顺行途径。CXCR 4同源二聚体依赖于Rabs 2、6和8进行顺行转运，而不管内源性CD 4的存在。当CD 4不存在时，CCR 5同源二聚体依赖于Rabs 1和11，但当CD 4存在时，依赖于Rabs 1和8。有趣的是，与CCR 5同源二聚体相似，CXCR 4-CCR 5异源二聚体依赖于Rab 1和11，但当CD 4不存在时也需要Rab 2，当CD 4存在时仅需要Rab 1。我们的研究结果表明，虽然组成的异二聚体复合物的受体是相同的，在同二聚体的，异二聚体的交通和信号不同于每个同二聚体。我们的研究表明，考虑受体异源二聚体作为不同的信号实体，应仔细和单独的特点的重要性。(C)2011 Elsevier Inc. All rights reserved.
Much is known about G protein coupled receptor trafficking and internalization following agonist stimulation. However, much less is known about outward trafficking of receptors from synthesis in the endoplasmic reticulum to the plasma membrane, or the role that trafficking might play in the assembly of receptor signaling complexes, important for targeting, specificity, and rapidity of subsequent signaling events. Up to now, very little is understood about receptor hetero-oligomers other than the fact that their assembly is done rapidly after biosynthesis. In our study we use bimolecular fluorescence complementation to selectively follow receptor dimers when expressed in Jurkat cells in order to clarify the trafficking itinerary those receptors follow to reach the plasma membrane and the resulting effect on signal transduction. CXCR4 and CCR5, previously shown to form both homo and hetero-oligomers, were used as our model to understand the specificities of trafficking along the anterograde pathway. The CXCR4 homodimer relies on Rabs2, 6 and 8 for anterograde transport regardless of the presence of endogenous CD4. The CCR5 homodimer relies on Rabs1 and 11 when CD4 is absent, but Rabs1 and 8 when CD4 was present. Interestingly, similar to the CCR5 homodimer, the CXCR4-CCR5 heterodimer relied on Rabs1 and 11 but also required Rab2 when CD4 was absent, and only Rab 1 when CD4 was present. Our results demonstrate that, although the receptors composing the heterodimeric complex are the same as in the homodimeric ones, the heterodimer traffics and signals differently than each homodimer. Our study demonstrates the importance of considering the receptor heterodimers as distinct signaling entities that should be carefully and individually characterized. (C) 2011 Elsevier Inc. All rights reserved.