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

Journal of Cell Science
I-Hsuan WangUrs F Greber

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 ...Continue Reading

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Citations

Apr 20, 2018·Viruses·Robert WitteUrs F Greber
Jun 16, 2017·Journal of Virology·Mojgan H Naghavi, Derek Walsh
Jul 10, 2019·Annual Review of Virology·Urs F Greber, Justin W Flatt
Nov 24, 2019·FEBS Letters·Noémie Pied, Harald Wodrich
Nov 12, 2019·FEBS Letters·Paloma Hidalgo, Ramón A Gonzalez
Mar 28, 2020·FEBS Letters·Julian SchererRichard B Vallee
Apr 9, 2019·Open Biology·Justin W Flatt, Sarah J Butcher
Mar 13, 2020·Journal of Virology·Irene Carlon-AndresHarald Wodrich
Sep 13, 2020·Journal of Cell Science·Maarit SuomalainenUrs F Greber
Jan 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Stephanie L SarbanesCharles M Rice
Apr 24, 2021·Current Opinion in Virology·Urs F Greber, Alfonso Gomez-Gonzalez
Aug 29, 2021·Viruses·Maarit Suomalainen, Urs F Greber

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