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Sec16A is critical for both conventional and unconventional secretion of CFTR.

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.

SUBMITTER: Piao H

PROVIDER: S-EPMC5220342 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Sec16A is critical for both conventional and unconventional secretion of CFTR.

Piao He H Kim Jiyoon J Noh Shin Hye SH Kweon Hee-Seok HS Kim Joo Young JY Lee Min Goo MG

Scientific reports 20170109

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 unconvention ...[more]

PMID: 28067262

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Dataset Information

Sec16A is critical for both conventional and unconventional secretion of CFTR.

Publications

Sec16A is critical for both conventional and unconventional secretion of CFTR.

Similar Datasets

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