Storez Hélène, Scott Mark G H, Issafras Hassan, Burtey Anne, Benmerah Alexandre, Muntaner Olivier, Piolot Tristan, Tramier Marc, Coppey-Moisan Maité, Bouvier Michel, Labbé-Jullié Catherine, Marullo Stefano
Department of Cell Biology, Institut Cochin, Paris, F-75014 France.
J Biol Chem. 2005 Dec 2;280(48):40210-5. doi: 10.1074/jbc.M508001200. Epub 2005 Sep 30.
Arrestins are important proteins, which regulate the function of serpentine heptahelical receptors and contribute to multiple signaling pathways downstream of receptors. The ubiquitous beta-arrestins are believed to function exclusively as monomers, although self-association is assumed to control the activity of visual arrestin in the retina, where this isoform is particularly abundant. Here the oligomerization status of beta-arrestins was investigated using different approaches, including co-immunoprecipitation of epitope-tagged beta-arrestins and resonance energy transfer (BRET and FRET) in living cells. At steady state and at physiological concentrations, beta-arrestins constitutively form both homo- and hetero-oligomers. Co-expression of beta-arrestin2 and beta-arrestin1 prevented beta-arrestin1 accumulation into the nucleus, suggesting that hetero-oligomerization may have functional consequences. Our data clearly indicate that beta-arrestins can exist as homo- and hetero-oligomers in living cells and raise the hypothesis that the oligomeric state may regulate their subcellular distribution and functions.
抑制蛋白是重要的蛋白质，它们调节蛇形七螺旋受体的功能，并参与受体下游的多种信号通路。普遍存在的β抑制蛋白被认为仅以单体形式发挥作用，尽管人们认为自我缔合控制着视网膜中视觉抑制蛋白的活性，在视网膜中这种异构体特别丰富。在这里，我们使用了不同的方法来研究β抑制蛋白的寡聚化状态，包括在活细胞中对表位标记的β抑制蛋白进行共免疫沉淀以及共振能量转移（生物发光共振能量转移和荧光共振能量转移）。在稳态和生理浓度下，β抑制蛋白组成性地形成同型和异型寡聚体。β抑制蛋白2和β抑制蛋白1的共表达阻止了β抑制蛋白1在细胞核中的积累，这表明异型寡聚化可能具有功能后果。我们的数据清楚地表明，β抑制蛋白可以在活细胞中以同型和异型寡聚体的形式存在，并提出了寡聚状态可能调节其亚细胞分布和功能的假设。
