O-GlcNAc modification of nuclear pore complexes accelerates bidirectional transport

被引:18
作者
Yoo, Tae Yeon [1 ]
Mitchison, Timothy J. [1 ]
机构
[1] Harvard Med Sch, Blavatnik Inst, Dept Syst Biol, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
WHEAT-GERM-AGGLUTININ; NUCLEOCYTOPLASMIC TRANSPORT; UNNATURAL MONOSACCHARIDES; N-ACETYLGLUCOSAMINE; NUCLEOPORIN NUP153; CYTOSOLIC PROTEINS; GLYCOSYLATION; RAN; IMPORT; EXPORT;
D O I
10.1083/jcb.202010141
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Macromolecular transport across the nuclear envelope depends on facilitated diffusion through nuclear pore complexes (NPCs). The interior of NPCs contains a permeability barrier made of phenylalanine-glycine (FG) repeat domains that selectively facilitates the permeation of cargoes bound to nuclear transport receptors (NTRs). FG-repeat domains in NPCs are a major site of O-linked N-acetylglucosamine (O-GlcNAc) modification, but the functional role of this modification in nucleocytoplasmic transport is unclear. We developed high-throughput assays based on optogenetic probes to quantify the kinetics of nuclear import and export in living human cells. We found that increasing O-GlcNAc modification of the NPC accelerated NTR-facilitated transport of proteins in both directions, and decreasing modification slowed transport. Superresolution imaging revealed strong enrichment of O-GlcNAc at the FG-repeat barrier. O-GlcNAc modification also accelerated passive permeation of a small, inert protein through NPCs. We conclude that O-GlcNAc modification accelerates nucleocytoplasmic transport by enhancing the nonspecific permeability of the FG-repeat barrier, perhaps by steric inhibition of interactions between FG repeats.
引用
收藏
页数:18
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