期刊
JOURNAL OF CELL BIOLOGY
卷 211, 期 2, 页码 323-337出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201505123
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资金
- National Institutes of Health [R01GM101975, P01GM105536]
Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection similar to 5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170 mediated capture to initiate transport in primary human cells.
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