| First Author | Song X | Year | 2013 |
| Journal | Cell Signal | Volume | 25 |
| Issue | 12 | Pages | 2613-24 |
| PubMed ID | 24012956 | Mgi Jnum | J:280138 |
| Mgi Id | MGI:6369281 | Doi | 10.1016/j.cellsig.2013.08.022 |
| Citation | Song X, et al. (2013) Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant. Cell Signal 25(12):2613-24 |
| abstractText | Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal shutoff. We show that high transgenic expression of an arrestin-1 mutant with enhanced rhodopsin binding and impaired oligomerization causes apoptotic rod death in mice. Dark rearing does not prevent mutant-induced cell death, ruling out the role of arrestin complexes with light-activated rhodopsin. Similar expression of WT arrestin-1 that robustly oligomerizes, which leads to only modest increase in the monomer concentration, does not affect rod survival. Moreover, WT arrestin-1 co-expressed with the mutant delays retinal degeneration. Thus, arrestin-1 mutant directly affects cell survival via binding partner(s) other than light-activated rhodopsin. Due to impaired self-association of the mutant its high expression dramatically increases the concentration of the monomer. The data suggest that monomeric arrestin-1 is cytotoxic and WT arrestin-1 protects rods by forming mixed oligomers with the mutant and/or competing with it for the binding to non-receptor partners. Thus, arrestin-1 self-association likely serves to keep low concentration of the toxic monomer. The reduction of the concentration of harmful monomer is an earlier unappreciated biological function of protein oligomerization. |
