15 research outputs found
The nuclear export factor CRM1 controls juxta-nuclear microtubule-dependent virus transport
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 infectio