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Sec16A is critical for both conventional and unconventional secretion of CFTR

Authors
 He Piao  ;  Jiyoon Kim  ;  Shin Hye Noh  ;  Hee-Seok Kweon  ;  Joo Young Kim  ;  Min Goo Lee 
Citation
 Scientific Reports, Vol.7 : 39887-39887, 2017 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2017
Abstract
CFTR is a transmembrane protein that reaches the cell surface via the conventional Golgi mediated secretion pathway. Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type CFTR and the disease-causing ΔF508-CFTR, which has folding and trafficking defects. Here, we show that Sec16A, the key regulator of conventional ER-to-Golgi transport, plays a critical role in the ER exit of protein cargos during unconventional secretion. In an initial gene silencing screen, Sec16A knockdown abolished the unconventional secretion of wild-type and ΔF508-CFTR induced by ER-to-Golgi blockade, whereas the knockdown of other COPII-related components did not. Notably, during unconventional secretion, Sec16A was redistributed to cell periphery and associated with GRASP55 in mammalian cells. Molecular and morphological analyses revealed that IRE1α-mediated signaling is an upstream regulator of Sec16A during ER-to-Golgi blockade or ER stress associated unconventional secretion. These findings highlight a novel function of Sec16A as an essential mediator of ER stress-associated unconventional secretion.
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DOI
10.1038/srep39887.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실)
Yonsei Authors
김주영(Kim, Joo Young) ORCID logo https://orcid.org/0000-0003-2623-1491
김지윤(Kim, Ji Yoon)
노신혜(Noh, Shin Hye)
박학(Piao He) ORCID logo https://orcid.org/0000-0002-1817-3167
이민구(Lee, Min Goo) ORCID logo https://orcid.org/0000-0001-7436-012X
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154094
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