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J Cell Sci. 2017 Jul 1;130(13):2185-2195. doi: 10.1242/jcs.203794. Epub 2017 May 17.

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

Author information

1
Department of Molecular Life Sciences, University of Zürich, 8057 Zurich, Switzerland.
2
Department of Bioinformatics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
3
Molecular Life Sciences Graduate School, ETH and University of Zürich, 8057 Zurich, Switzerland.
4
Department of Molecular Life Sciences, University of Zürich, 8057 Zurich, Switzerland urs.greber@imls.uzh.ch.

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 (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.

KEYWORDS:

Adenovirus; CRM1; Fluorescence microscopy; Intracellular transport; Machine learning; Microtubule; Virus entry

PMID:
28515232
DOI:
10.1242/jcs.203794
[Indexed for MEDLINE]
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