Presence of β-arrestin in cellular inclusions in metamphetamine-treated PC12 cells

Cellular inclusions containing ubiquitin and α-synuclein were observed in PC12 cells treated with metamphetamine (MA). To study the possible involvement of β-arrestin in inclusion formation, we treated PC12 cells with MA for different times and analyzed the ubiquitin proteosome pathway (UPP). We found that β-arrestin is ubiquitinated in the MA-treated PC12 cell line. The involvement of β-arrestin in UPP was further supported by electron microscopy and by confocal microscopy, which documented the presence of β-arrestin in these Lewy body-like inclusions. Our experiments reveal an interesting and previously unappreciated connection between β-arrestin and ubiquitination and suggest that β-arrestin could be involved in the development of the inclusion bodies.