Back to Search Start Over

Intermolecular disulfide bonds among nucleoporins regulate karyopherin-dependent nuclear transport

Authors :
Shige H. Yoshimura
Shotaro Otsuka
Kunio Takeyasu
Mariko Taga
Masahiro Kumeta
Source :
Journal of Cell Science.
Publication Year :
2013
Publisher :
The Company of Biologists, 2013.

Abstract

Disulfide (S-S) bonds play important roles in the regulation of protein function and cellular stress responses. In this study, we demonstrate that distinct sets of nucleoporins (Nups), components of the nuclear pore complex (NPC), form S-S bonds and regulate nuclear transport through the NPC. Kinetic analysis of importin β demonstrated that the permeability of the NPC was increased by dithiothreitol treatment and reduced by oxidative stress. The permeability of small proteins such as GFP was not affected by either oxidative stress or a reducing reagent. Immunoblot analysis revealed that the oxidative stress significantly induced S-S bond formation in Nups358, 155, 153, and 62 but not 88 and 160. The direct involvement of cysteine residues in the formation of S-S bonds was confirmed by mutating conserved cysteine residues in Nup62, which abolished the formation of S-S bonds and enhanced the permeability of the NPC. Knocking down Nup62 reduced the stress-inducible S-S bonds of Nup155, suggesting that Nups62 and 155 are covalently coupled via S-S bonds. From these results, we propose that the inner channel of the NPC is somehow insulated from the cytoplasm, and is more sensitive than the cytoplasm to the intracellular redox state.

Details

ISSN :
14779137 and 00219533
Database :
OpenAIRE
Journal :
Journal of Cell Science
Accession number :
edsair.doi.dedup.....869e2601103b2fd04556d9f6c258d6e4
Full Text :
https://doi.org/10.1242/jcs.124172