| First Author | Manson ME | Year | 2012 |
| Journal | J Lipid Res | Volume | 53 |
| Issue | 7 | Pages | 1268-76 |
| PubMed ID | 22523395 | Mgi Jnum | J:186267 |
| Mgi Id | MGI:5431282 | Doi | 10.1194/jlr.M021972 |
| Citation | Manson ME, et al. (2012) Regulatory role of beta-arrestin-2 in cholesterol processing in cystic fibrosis epithelial cells. J Lipid Res 53(7):1268-76 |
| abstractText | Cystic fibrosis (CF) cells exhibit an increase in the protein expression of beta-arrestin-2 (betaarr2) coincident with perinuclear accumulation of free cholesterol. Arrestins are proteins that both serve as broad signaling regulators and contribute to G-protein coupled receptor internalization after agonist stimulation. The hypothesis of this study is that betaarr2 is an important component in the mechanisms leading to cholesterol accumulation characteristic of CF cells. To test this hypothesis, epithelial cells stably expressing GFP-tagged betaarr2 (betaarr2-GFP) and respective GFP-expressing control cells (cont-GFP) were analyzed by filipin staining. The betaarr2-GFP cells show a late endosomal/lysosomal cholesterol accumulation that is identical to that seen in CF cells. This betaarr2-mediated accumulation is sensitive to Rp-cAMPS treatment, and depleting betaarr2 expression in CF-model cells by shRNA alleviates cholesterol accumulation compared with controls. Cftr/betaarr2 double knockout mice also exhibit wild-type (WT) levels of cholesterol synthesis, and WT profiles of signaling protein expression have previously been shown to be altered in CF due to cholesterol-related pathways. These data indicate a significant regulatory role for betaarr2 in the development of CF-like cholesterol accumulation and give further insight into cholesterol processing mechanisms. An impact of betaarr2 expression on Niemann-Pick type C-1 (NPC1)-containing organelle movement is proposed as the mechanism of betaarr2-mediated alterations on cholesterol processing. It is concluded that betaarr2 expression contributes to altered cholesterol trafficking observed in CF cells. |
