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Two motifs with different function regulate the anterograde transport of the adiponectin receptor 1

机译:具有不同功能的两个基序调节脂联素受体1的顺行转运

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摘要

The anterograde trafficking of GPCR has been described as a tightly controlled process involving specific amino acid sequences that mediate the receptor transport. In this study, we investigated whether the cell surface delivery of the adiponectin receptor 1, a newly identified class of heptahelix receptors different from G protein-coupled receptors, is regulated. Sequential N-terminal deletion revealed that the export of the AdipoR1 from the endoplasmic reticulum (ER) is controlled by distinct parts of the receptor N-terminus. Strong evidence is provided that the ER exit is mediated by two specific sequences, a F(X) _3F(X) _3F and a D(X) _3LL motif. Disruption of these motifs led to a substantial accumulation of the AdipoR1 in the ER. Mutation of similar motifs in the AdipoR1 C-terminus did not result in aberrant receptor localization, suggesting that these motifs are sequence and position specific to the AdipoR1 N-terminus. Further analysis of the regulation mechanism identified an interaction with the chaperone BiP and additionally, strong evidence is provided that both motifs exert different biological function in the AdipoR1 ER export. In conclusion, our data demonstrate that the receptor transport shares similar ER exit motifs although AdipoR are structurally different from GPCR. However, since even two specific sequences are identified, the anterograde trafficking of the AdipoR1 seems to be regulated in a more complex manner.
机译:GPCR的顺行转运已被描述为一个严格控制的过程,涉及介导受体转运的特定氨基酸序列。在这项研究中,我们调查了脂联素受体1(一种新鉴定的不同于G蛋白偶联受体的七螺旋体受体)的细胞表面传递是否受到调节。顺序的N末端删除显示AdipoR1从内质网(ER)的出口受受体N末端的不同部分控制。有力证据表明,ER出口由两个特定序列介导,即F(X)_3F(X)_3F和D(X)_3LL基序。这些基序的破坏导致AdipoR1在ER中大量积累。 AdipoR1 C末端相似基序的突变不会导致异常的受体定位,这表明这些基序是AdipoR1 N末端特异的序列和位置。对调节机制的进一步分析确定了与伴侣BiP的相互作用,此外,有力的证据表明这两个基序在AdipoR1 ER的输出中发挥了不同的生物学功能。总之,我们的数据表明,尽管AdipoR在结构上与GPCR不同,但受体转运具有相似的ER出口基序。然而,由于甚至鉴定出两个特定序列,AdipoR1的顺行运输似乎以更复杂的方式受到调控。

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