Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.cell.2011.07.021
Title: | Rescue of Δf508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway | Authors: | Gee, H.Y. Noh, S.H. Tang, B.L. Kim, K.H. Lee, M.G. |
Issue Date: | 2-Sep-2011 | Citation: | Gee, H.Y., Noh, S.H., Tang, B.L., Kim, K.H., Lee, M.G. (2011-09-02). Rescue of Δf508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway. Cell 146 (5) : 746-760. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cell.2011.07.021 | Abstract: | The most prevalent disease-causing mutation of CFTR is the deletion of Phe508 (ΔF508), which leads to defects in conventional Golgi-mediated exocytosis and cell surface expression. We report that ΔF508-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 ΔF508-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 ΔF508-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. © 2011 Elsevier Inc. | Source Title: | Cell | URI: | http://scholarbank.nus.edu.sg/handle/10635/109591 | ISSN: | 00928674 | DOI: | 10.1016/j.cell.2011.07.021 |
Appears in Collections: | Staff Publications |
Show full item record
Files in This Item:
There are no files associated with this item.
SCOPUSTM
Citations
227
checked on Feb 3, 2023
WEB OF SCIENCETM
Citations
220
checked on Feb 3, 2023
Page view(s)
192
checked on Feb 2, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.