| First Author | Gee HY | Year | 2011 |
| Journal | Cell | Volume | 146 |
| Issue | 5 | Pages | 746-60 |
| PubMed ID | 21884936 | Mgi Jnum | J:176213 |
| Mgi Id | MGI:5289719 | Doi | 10.1016/j.cell.2011.07.021 |
| Citation | Gee HY, et al. (2011) Rescue of DeltaF508-CFTR Trafficking via a GRASP-Dependent Unconventional Secretion Pathway. Cell 146(5):746-60 |
| abstractText | The most prevalent disease-causing mutation of CFTR is the deletion of Phe508 (DeltaF508), which leads to defects in conventional Golgi-mediated exocytosis and cell surface expression. We report that DeltaF508-CFTR surface expression can be rescued in vitro and in vivo by directing it to an unconventional GRASP-dependent secretion pathway. An integrated molecular and physiological analysis indicates that mechanisms associated with ER stress induce cell surface trafficking of the ER core-glycosylated wild-type and DeltaF508-CFTR via the GRASP-dependent pathway. Phosphorylation of a specific site of GRASP and the PDZ-based interaction between GRASP and CFTR are critical for this unconventional surface trafficking. Remarkably, transgenic expression of GRASP in DeltaF508-CFTR mice restores CFTR function and rescues mouse survival without apparent toxicity. These findings provide insight into how unconventional protein secretion is activated, and offer a potential therapeutic strategy for the treatment of cystic fibrosis and perhaps diseases stemming from other misfolded proteins. |
