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Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy
Author(s) -
Liu GuanTing,
Kung HsiuNi,
Chen ChungKuan,
Huang Cheng,
Wang YungLi,
Yu ChengPu,
Lee ChungPei
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701253r
Subject(s) - autophagy , microbiology and biotechnology , vesicle , nuclear pore , vacuole , nuclear transport , cytoplasm , autophagosome , chemistry , biology , inner membrane , vesicular transport protein , cell nucleus , biochemistry , membrane , mitochondrion , apoptosis
Although a vesicular nucleocytoplasmic transport system is believed to exist in eukaryotic cells, the features of this pathway are mostly unknown. Here, we report that the BFRF1 protein of the Epstein‐Barr virus improves vesicular transport of nuclear envelope (NE) to facilitate the translocation and clearance of nuclear components. BFRF1 expression induces vesicles that selectively transport nuclear components to the cytoplasm. With the use of aggregation‐prone proteins as tools, we found that aggregated nuclear proteins are dispersed when these BFRF1‐induced vesicles are formed. BFRF1‐containing vesicles engulf the NE‐associated aggregates, exit through from the NE, and putatively fuse with autophagic vacuoles. Chemical treatment and genetic ablation of autophagy‐related factors indicate that autophagosome formation and autophagy‐linked FYVE protein‐mediated autophagic proteolysis are involved in this selective clearance of nuclear proteins. Remarkably, vesicular transport, elicited by BFRF1, also attenuated nuclear aggregates accumulated in neuroblastoma cells. Accordingly, induction of NE‐derived vesicles by BFRF1 facilitates nuclear protein translocation and clearance, suggesting that autophagy‐coupled transport of nucleus‐derived vesicles can be elicited for nuclear component catabolism in mammalian cells.—Liu, G.‐T., Kung, H.‐N., Chen, C.‐K., Huang, C., Wang, Y.‐L., Yu, C.‐P., Lee, C.‐P. Improving nuclear envelope dynamics by EBV BFRF1 facilitates intranuclear component clearance through autophagy. FASEB J. 32, 3968–3983 (2018). www.fasebj.org