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Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export

Fornerod, Maarten; Bernad, Rafael; Engelsma, Dieuwke; Sanderson, Helen; Pickersgill, Helen; Fornerod, Maarten

Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export Thumbnail


Authors

Maarten Fornerod

Rafael Bernad

Dieuwke Engelsma

Helen Pickersgill

Maarten Fornerod



Abstract

The nuclear pore complex (NPC) conducts macromolecular transport to and from the nucleus and provides a kinetic/hydrophobic barrier composed of phenylalanine-glycine (FG) repeats. Nuclear transport is achieved through permeation of this barrier by transport receptors. The transport receptor CRM1 facilitates export of a large variety of cargoes. Export of the preribosomal 60 S subunit follows this pathway through the adaptor protein NMD3. Using RNA interference, we depleted two FG-containing cytoplasmically oriented NPC complexes, Nup214-Nup88 and Nup358, and investigated CRM1-mediated export. A dramatic defect in NMD3-mediated export of preribosomes was found in Nup214-Nup88-depleted cells, whereas only minor export defects were evident in other CRM1 cargoes or upon depletion of Nup358. We show that the large C-terminal FG domain of Nup214 is not accessible to freely diffusing molecules from the nucleus, indicating that it does not conduct 60 S preribosomes through the NPC. Consistently, derivatives of Nup214 lacking the FG-repeat domain rescued the 60 S export defect. We show that the coiled-coil region of Nup214 is sufficient for 60 S nuclear export, coinciding with recruitment of Nup88 to the NPC. Our data indicate that Nup214 plays independent roles in NPC function by participating in the kinetic/hydrophobic barrier through its FG-rich domain and by enabling NPC gating through association with Nup88. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Citation

Fornerod, M., Bernad, R., Engelsma, D., Sanderson, H., Pickersgill, H., & Fornerod, . M. (2006). Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export. Journal of Biological Chemistry, 281(28), 19378-19386. https://doi.org/10.1074/jbc.M512585200

Journal Article Type Article
Acceptance Date Feb 24, 2006
Online Publication Date May 4, 2006
Publication Date Jul 14, 2006
Deposit Date Jun 22, 2021
Publicly Available Date Mar 28, 2024
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 281
Issue 28
Pages 19378-19386
DOI https://doi.org/10.1074/jbc.M512585200
Public URL https://uwe-repository.worktribe.com/output/7483609

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