Molla-Herman Anahi, Boularan Cedric, Ghossoub Rania, Scott Mark G H, Burtey Anne, Zarka Marion, Saunier Sophie, Concordet Jean-Paul, Marullo Stefano, Benmerah Alexandre
Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Paris, France.
PLoS One. 2008;3(11):e3728. doi: 10.1371/journal.pone.0003728. Epub 2008 Nov 14.
The primary cilium is a sensory organelle generated from the centrosome in quiescent cells and found at the surface of most cell types, from where it controls important physiological processes. Specific sets of membrane proteins involved in sensing the extracellular milieu are concentrated within cilia, including G protein coupled receptors (GPCRs). Most GPCRs are regulated by beta-arrestins, betaarr1 and betaarr2, which control both their signalling and endocytosis, suggesting that betaarrs may also function at primary cilium.
METHODOLOGY/PRINCIPAL FINDINGS: In cycling cells, betaarr2 was observed at the centrosome, at the proximal region of the centrioles, in a microtubule independent manner. However, betaarr2 did not appear to be involved in classical centrosome-associated functions. In quiescent cells, both in vitro and in vivo, betaarr2 was found at the basal body and axoneme of primary cilia. Interestingly, betaarr2 was found to interact and colocalize with 14-3-3 proteins and Kif3A, two proteins known to be involved in ciliogenesis and intraciliary transport. In addition, as suggested for other centrosome or cilia-associated proteins, betaarrs appear to control cell cycle progression. Indeed, cells lacking betaarr2 were unable to properly respond to serum starvation and formed less primary cilia in these conditions.
CONCLUSIONS/SIGNIFICANCE: Our results show that betaarr2 is localized to the centrosome in cycling cells and to the primary cilium in quiescent cells, a feature shared with other proteins known to be involved in ciliogenesis or primary cilium function. Within cilia, betaarr2 may participate in the signaling of cilia-associated GPCRs and, therefore, in the sensory functions of this cell "antenna".
初级纤毛是一种感觉细胞器，由静止细胞中的中心体产生，存在于大多数细胞类型的表面，它从该位置控制重要的生理过程。参与感知细胞外环境的特定膜蛋白集集中在纤毛内，包括G蛋白偶联受体（GPCRs）。大多数GPCRs受β-抑制蛋白βarr1和βarr2调节，它们控制GPCRs的信号传导和内吞作用，这表明β-抑制蛋白也可能在初级纤毛中发挥作用。
方法/主要发现：在循环细胞中，观察到βarr2以微管非依赖的方式存在于中心体、中心粒的近端区域。然而，βarr2似乎不参与经典的中心体相关功能。在体外和体内的静止细胞中，发现βarr2存在于初级纤毛的基体和轴丝中。有趣的是，发现βarr2与14-3-3蛋白和Kif3A相互作用并共定位，这两种蛋白已知参与纤毛发生和纤毛内运输。此外，正如对其他中心体或纤毛相关蛋白的推测，β-抑制蛋白似乎控制细胞周期进程。确实，缺乏βarr2的细胞在血清饥饿时无法正常反应，并且在这些条件下形成的初级纤毛较少。
结论/意义：我们的结果表明，βarr2在循环细胞中定位于中心体，在静止细胞中定位于初级纤毛，这一特征与已知参与纤毛发生或初级纤毛功能的其他蛋白相同。在纤毛内，βarr2可能参与纤毛相关GPCRs的信号传导，因此参与这个细胞“天线”的感觉功能。
