| First Author | Shu X | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 10 | Pages | 1680-9 |
| PubMed ID | 16600989 | Mgi Jnum | J:326908 |
| Mgi Id | MGI:7327239 | Doi | 10.1093/hmg/ddl091 |
| Citation | Shu X, et al. (2006) Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5. Hum Mol Genet 15(10):1680-9 |
| abstractText | Late-onset retinal macular degeneration (L-ORMD) is an autosomal dominant condition resembling age-related macular degeneration (AMD) in which a key pathological feature is a thick extracellular sub-retinal pigment epithelial (RPE) deposit. L-ORMD is caused by mutation in the C1QTNF5 (CTRP5) short-chain collagen gene, but the disease mechanism is unknown. Here, we first show that wild-type C1QTNF5 is secreted, whereas mutant C1QTNF5 is misfolded and retained within the endoplasmic reticulum (ER). Secondly, the ER retained mutant protein has a shorter half-life than wild-type C1QTNF5 and is preferentially degraded by proteasomes. Thirdly, C1QTNF5 is shown to interact with the membrane-type frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein pull-down and co-immunoprecipitation assays and RPE co-localization. These data suggest that L-ORMD is due to insufficient levels of secreted C1QTNF5, compromised RPE cell function resulting from ER retention of the mutant protein or both mechanisms. |
