Importin-β modulates the permeability of the nuclear pore complex in a Ran-dependent manner

被引:107
作者
Lowe, Alan R. [1 ,2 ,3 ,4 ,5 ,6 ]
Tang, Jeffrey H. [4 ,5 ,6 ,7 ,8 ,9 ,10 ]
Yassif, Jaime [4 ,5 ,6 ,10 ]
Graf, Michael [11 ]
Huang, William Y. C. [12 ]
Groves, Jay T. [5 ,6 ,10 ,12 ,13 ]
Weis, Karsten [8 ,9 ]
Liphardt, Jan T. [4 ,5 ,6 ,7 ,8 ,10 ,13 ]
机构
[1] UCL, Inst Struct & Mol Biol, London, England
[2] Birkbeck Coll, London, England
[3] UCL, London Ctr Nanotechnol, London, England
[4] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA
[5] Univ Calif Berkeley, QB3, Berkeley, CA 94720 USA
[6] Univ Calif Berkeley, Bay Area Phys Sci, Ctr Oncol, Berkeley, CA 94720 USA
[7] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[8] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[9] Eidgenoss Tech Hsch Zurich, Inst Biochem, Zurich, Switzerland
[10] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA
[11] Ecole Polytech Fed Lausanne, Sect Life Sci & Technol, Lausanne, Switzerland
[12] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Chem, Berkeley, CA 94720 USA
[13] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
PROTEIN IMPORT; NUCLEOPORIN NUP153; KINETIC-ANALYSIS; SINGLE; TRANSPORT; BINDING; TRANSLOCATION; RECEPTOR; PHOSPHORYLATION; IDENTIFICATION;
D O I
10.7554/eLife.04052
中图分类号
Q [生物科学];
学科分类号
090105 [作物生产系统与生态工程];
摘要
Soluble karyopherins of the importin-beta (imp beta) family use RanGTP to transport cargos directionally through the nuclear pore complex (NPC). Whether imp beta or RanGTP regulate the permeability of the NPC itself has been unknown. In this study, we identify a stable pool of imp beta at the NPC. A subpopulation of this pool is rapidly turned-over by RanGTP, likely at Nup153. imp beta, but not transportin-1 (TRN1), alters the pore's permeability in a Ran-dependent manner, suggesting that imp beta is a functional component of the NPC. Upon reduction of Nup153 levels, inert cargos more readily equilibrate across the NPC yet active transport is impaired. When purified imp beta or TRN1 are mixed with Nup153 in vitro, higher-order, multivalent complexes form. RanGTP dissolves the imp beta eNup153 complexes but not those of TRN1.Nup153. We propose that imp beta and Nup153 interact at the NPC's nuclear face to form a Ran-regulated mesh that modulates NPC permeability.
引用
收藏
页数:24
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