0 160

Cited 2 times in

Specific autophagy and ESCRT components participate in the unconventional secretion of CFTR

 Shin Hye Noh  ;  Heon Yung Gee  ;  Yonjung Kim  ;  He Piao  ;  Jiyoon Kim  ;  Chung Min Kang  ;  Gahyung Lee  ;  Inhee Mook-Jung  ;  Yangsin Lee  ;  Jin Won Cho  ;  Min Goo Lee 
 AUTOPHAGY, Vol.14(10) : 1761-1778, 2018 
Journal Title
Issue Date
Autophagy ; CFTR ; ESCRT ; GORASP2/GRASP55 ; MVB12B ; unconventional trafficking
The most common mutation in cystic fibrosis patients is a phenylalanine deletion at position 508 (ΔF508) in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. This mutation impairs cell-surface trafficking of CFTR. During cellular stress, core-glycosylated CFTRΔF508 is transported to the cell surface from the endoplasmic reticulum (ER) via an unconventional route that bypasses the Golgi. However, the mechanisms for this unconventional secretory pathway of CFTR are not well delineated. Here, we report that components of the macroautophagy/autophagy and ESCRT (endosomal sorting complex required for transport) pathways are involved in unconventional secretion of CFTR. In mammalian cells, we found that autophagic pathways were modulated by conditions that also stimulate unconventional secretion, namely ER stress and an ER-to-Golgi transport blockade. Additionally, we found that knockdown of early autophagy components, ATG5 and ATG7, and treatment with pharmacological autophagy inhibitors, wortmannin and 3-methyladenine, abolished the unconventional secretion of CFTR that had been stimulated by ER stress and an ER-to-Golgi blockade. Interestingly, immunoelectron microscopy revealed that GORASP2/GRASP55, which mediates unconventional CFTR trafficking, is present in multivesicular bodies (MVB) and autophagosomal structures under ER stress conditions. A custom small-interfering RNA screen of mammalian ESCRT proteins that mediate MVB biogenesis showed that silencing of some ESCRTs, including MVB12B, inhibited unconventional CFTRΔF508 secretion. Furthermore, MVB12B overexpression partially rescued cell-surface expression and Cl- channel function of CFTRΔF508. Taken together, these results suggest that components involved in early autophagosome formation and the ESCRT/MVB pathway play a key role in the stress-induced unconventional secretion of CFTR.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chung Min(강정민) ORCID logo https://orcid.org/0000-0001-7813-3741
Kim, Yon Jung(김연정) ORCID logo https://orcid.org/0000-0003-0251-8711
Noh, Shin Hye(노신혜)
Piao He(박학) ORCID logo https://orcid.org/0000-0002-1817-3167
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
Gee, Heon Yung(지헌영) ORCID logo https://orcid.org/0000-0002-8741-6177
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.