Wang, I-H;
Burckhardt, CJ;
Yakimovich, A;
Morf, MK;
Greber, UF;
(2017)
The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport.
Journal of Cell Science
, 130
(13)
pp. 2185-2195.
10.1242/jcs.203794.
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Abstract
Transport of large cargo through the cytoplasm requires motor proteins and polarized filaments. Viruses that replicate in the nucleus of post-mitotic cells use microtubules and the dynein–dynactin motor to traffic to the nuclear membrane and deliver their genome through nuclear pore complexes (NPCs) into the nucleus. How virus particles (virions) or cellular cargo are transferred from microtubules to the NPC is unknown. Here, we analyzed trafficking of incoming cytoplasmic adenoviruses by single-particle tracking and superresolution microscopy. We provide evidence for a regulatory role of CRM1 (chromosome-region-maintenance-1; also known as XPO1, exportin-1) in juxta-nuclear microtubule-dependent adenovirus transport. Leptomycin B (LMB) abolishes nuclear targeting of adenovirus. It binds to CRM1, precludes CRM1–cargo binding and blocks signal-dependent nuclear export. LMB-inhibited CRM1 did not compete with adenovirus for binding to the nucleoporin Nup214 at the NPC. Instead, CRM1 inhibition selectively enhanced virion association with microtubules, and boosted virion motions on microtubules less than ∼2 µm from the nuclear membrane. The data show that the nucleus provides positional information for incoming virions to detach from microtubules, engage a slower microtubule-independent motility to the NPC and enhance infection
| Type: | Article |
|---|---|
| Title: | The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.203794 |
| Publisher version: | http://doi.org/10.1242/jcs.203794 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Adenovirus, Fluorescence microscopy, Virus entry, Microtubule, Intracellular transport, CRM1, Machine learning |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10040584 |
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