Actinin-1 binds to the C-terminus of A2B adenosine receptor (A2BAR) and enhances A2BAR cell-surface expression.
Actinin-1 binds to the C-terminus of A2B adenosine receptor (A2BAR) and enhances A2BAR cell-surface expression.
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Actinin-1 与 A2B 腺苷受体 (A2BAR) 的 C 末端结合并增强 A2BAR 细胞表面表达。
DOI：
10.1042/bcj20160272
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Huang,Pingbo
中科院分区：
文献类型：
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作者：
Sun,Ying;Hu,Wenbao;Yu,Xiaojie;Liu,Zhengzhao;Tarran,Robert;Ravid,Katya;Huang,Pingbo
A2 BAR（A2 Badenosine receptor，A2 B腺苷受体）参与多种生理状态，如过敏性或炎症性疾病、血管舒张、细胞生长和上皮细胞电解质分泌。对于介导A2 BAR的蛋白质-蛋白质相互作用，受体的C-末端被认为是至关重要的。在本研究中，我们意外地发现A2 BAR C端的两个点突变（F297 A和R298 A）通过加速其降解而显著损害A2 BAR蛋白的表达。因此，我们测试了这两个点突变破坏A2 BAR与A2 BAR稳定性所必需的蛋白质的相互作用的假设。我们的研究结果表明，这两个突变破坏了A2 BAR与肌动蛋白-1，肌动蛋白相关蛋白的相互作用。此外，辅肌动蛋白-1结合稳定的全球和细胞表面的A2 BAR的表达。相比之下，辅肌动蛋白-4，另一种非肌肉辅肌动蛋白亚型，不结合A2 BAR。因此，我们的研究结果揭示了一个以前未确定的A2 BAR丰度的调节机制。
A2BAR (A2Badenosine receptor) has been implicated in several physiological conditions, such as allergic or inflammatory disorders, vasodilation, cell growth and epithelial electrolyte secretion. For mediating the protein–protein interactions of A2BAR, the receptor's C-terminus is recognized to be crucial. In the present study, we unexpectedly found that two point mutations in the A2BAR C-terminus (F297A and R298A) drastically impaired the expression of A2BAR protein by accelerating its degradation. Thus we tested the hypothesis that these two point mutations disrupt A2BAR's interaction with a protein essential for A2BAR stability. Our results show that both mutations disrupted the interaction of A2BAR with actinin-1, an actin-associated protein. Furthermore, actinin-1 binding stabilized the global and cell-surface expression of A2BAR. By contrast, actinin-4, another non-muscle actinin isoform, did not bind to A2BAR. Thus our findings reveal a previously unidentified regulatory mechanism of A2BAR abundance.