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The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport


Wang, I-Hsuan; Burckhardt, Christoph J; Yakimovich, Artur; Morf, Matthias K; Greber, Urs F (2017). The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport. Journal of Cell Science, 130(13):2185-2195.

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 super-resolution microscopy. We provide evidence for a regulatory role of CRM1/XPO1 (chromosome-region-maintenance-1, 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 about 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.

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 super-resolution microscopy. We provide evidence for a regulatory role of CRM1/XPO1 (chromosome-region-maintenance-1, 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 about 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:17 May 2017
Deposited On:06 Jun 2017 10:21
Last Modified:03 Jul 2017 01:03
Publisher:The Company of Biologists
ISSN:0021-9533
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1242/jcs.203794
PubMed ID:28515232

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