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

12 Citations (Scopus)

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

Fingerprint

Cell Nucleus Active Transport
Microtubules
Nuclear Pore
Viruses
Virion
Adenoviridae
Nuclear Envelope
Nuclear Export Signals
Nuclear Pore Complex Proteins
Dyneins
Microscopy
Cytoplasm
Chromosomes
Maintenance
Genome
Infection

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

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.

In: Journal of cell science, Vol. 130, No. 13, 01.07.2017, p. 2185-2195.

Research output: Contribution to journalArticle

Wang, I. Hsuan ; Burckhardt, Christoph J. ; Yakimovich, Artur ; Morf, Matthias K. ; Greber, Urs F. / The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport. In: Journal of cell science. 2017 ; Vol. 130, No. 13. pp. 2185-2195.
@article{6f0f5d151e9b4116a9c1fcaabdab9e86,
title = "The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport",
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.",
keywords = "Adenovirus, CRM1, Fluorescence microscopy, Intracellular transport, Machine learning, Microtubule, Virus entry",
author = "Wang, {I. Hsuan} and Burckhardt, {Christoph J.} and Artur Yakimovich and Morf, {Matthias K.} and Greber, {Urs F.}",
year = "2017",
month = "7",
day = "1",
doi = "10.1242/jcs.203794",
language = "English (US)",
volume = "130",
pages = "2185--2195",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "13",

}

TY - JOUR

T1 - The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport

AU - Wang, I. Hsuan

AU - Burckhardt, Christoph J.

AU - Yakimovich, Artur

AU - Morf, Matthias K.

AU - Greber, Urs F.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Adenovirus

KW - CRM1

KW - Fluorescence microscopy

KW - Intracellular transport

KW - Machine learning

KW - Microtubule

KW - Virus entry

UR - http://www.scopus.com/inward/record.url?scp=85021761787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021761787&partnerID=8YFLogxK

U2 - 10.1242/jcs.203794

DO - 10.1242/jcs.203794

M3 - Article

C2 - 28515232

AN - SCOPUS:85021761787

VL - 130

SP - 2185

EP - 2195

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 13

ER -