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

I. Hsuan Wang, Christoph J. Burckhardt, Artur Yakimovich, Matthias K. Morf, Urs F. Greber

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2185-2195
Number of pages11
JournalJournal of cell science
Volume130
Issue number13
DOIs
StatePublished - Jul 1 2017

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport'. Together they form a unique fingerprint.

  • Cite this