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Sec16A is critical for both conventional and unconventional secretion of CFTR

 He Piao  ;  Jiyoon Kim  ;  Shin Hye Noh  ;  Hee-Seok Kweon  ;  Joo Young Kim  ;  Min Goo Lee 
 SCIENTIFIC REPORTS, Vol.7 : 39887, 2017 
Journal Title
Issue Date
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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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Kim, Ji Yoon(김지윤)
Noh, Shin Hye(노신혜) ORCID logo https://orcid.org/0000-0003-3118-9240
Park, Hak(박학) ORCID logo https://orcid.org/0000-0002-1817-3167
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
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