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Rescue of ΔF508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway.

Title
 Rescue of ΔF508-CFTR trafficking via a GRASP-dependent unconventional secretion pathway. 
Authors
 Heon Yung Gee ; Shin Hye Noh ; Min Goo Lee ; Kyung Hwan Kim ; Bor Luen Tang 
Issue Date
2011
Journal Title
 Cell 
ISSN
 0092-8674 
Citation
 Cell, Vol.146(5) : 746~760, 2011 
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
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93566
DOI
10.1016/j.cell.2011.07.021
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0092867411008191
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