Beta‐Arrestin‐2 Binds to Nucleolar Organizing Regions With P2X7 Receptor Stimulation and During Cell Division

ABSTRACT Nonvisual arrestins , also known as Beta‐arrestins, are known for their diverse role in GPCR signal transduction. Here, we present evidence that Beta‐Arrestin‐2, a protein whose nuclear concentration is actively kept low, binds to Nucleolar Organizing Regions (NORs) on the metaphase chromosomes at the onset of cell division, after the disappearance of the nuclear membrane and stays bound therein in the daughter cells. After reformation of the nucleoli, it stays bound to the nucleoli until actively transported out of the reformed nucleus during interphase. This binding is unique for Beta‐Arrestin‐2, as the closely associated Beta‐Arrestin‐1 does not show this behavior at all. We also observed an intranuclear accumulation of Beta‐Arrestin‐2 after P2X7 receptor stimulation, similar to what has been described for Beta‐Arrestin‐2 after TRPV receptor stimulation. Present data identify a cyclic and well‐organized shuttling between NORs and the cytoplasm of Beta‐Arrestin‐2 during cell division, indicating a novel and unknown role for Beta‐Arrestin‐2 in cell physiology. Our data may also indicate a common intracellular signaling mechanism for a diverse group of receptors currently believed to function only as ligand‐gated channels (P2X7 and TRPV).