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
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