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Karyopherins regulate nuclear pore complex barrier and transport function

Kapinos, Larisa E. and Huang, Binlu and Rencurel, Chantal and Lim, Roderick Y. H.. (2017) Karyopherins regulate nuclear pore complex barrier and transport function. Journal of Cell Biology, 216 (11). pp. 3609-3624.

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Abstract

Nucleocytoplasmic transport is sustained by karyopherins (Kaps) and a Ran guanosine triphosphate (RanGTP) gradient that imports nuclear localization signal (NLS)–specific cargoes (NLS-cargoes) into the nucleus. However, how nuclear pore complex (NPC) barrier selectivity, Kap traffic, and NLS-cargo release are systematically linked and simultaneously regulated remains incoherent. In this study, we show that Kap α facilitates Kap β 1 turnover and occupancy at the NPC in a RanGTP-dependent manner that is directly coupled to NLS-cargo release and NPC barrier function. This is underpinned by the binding affinity of Kap β 1 to phenylalanine–glycine nucleoporins (FG Nups), which is comparable with RanGTP·Kap β 1, but stronger for Kap α ·Kap β 1. On this basis, RanGTP is ineffective at releasing standalone Kap β 1 from NPCs. Depleting Kap α ·Kap β 1 by RanGTP further abrogates NPC barrier function, whereas adding back Kap β 1 rescues it while Kap β 1 turnover softens it. Therefore, the FG Nups are necessary but insufficient for NPC barrier function. We conclude that Kaps constitute integral constituents of the NPC whose barrier, transport, and cargo release functionalities establish a continuum under a mechanism of Kap-centric control.
Faculties and Departments:05 Faculty of Science
05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nanobiology Argovia (Lim)
UniBasel Contributors:Lim, Roderick Y.H.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
ISSN:0021-9525
e-ISSN:1540-8140
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:12 Feb 2019 18:09
Deposited On:02 Oct 2017 14:30

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