Nucleocytoplasmic distribution of rabies virus P-protein is regulated by phosphorylation adjacent to C-terminal nuclear import and export signals

Gregory William Moseley, Richard Filmer, Michelle De Jesus, David Andrew Jans

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40 Citations (Scopus)


Nucleocytoplasmic distribution of the rabies virus phosphoprotein is implicated in the evasion of cellular antiviral mechanisms by rabies virus and has been reported to depend on an N-terminal nuclear export sequence and a C-terminal nuclear localization sequence. This paper identifies a second nuclear export sequence that is located between key residues of the nuclear localization sequence in the phosphoprotein C-terminal domain. The C-terminal domain confers predominantly nuclear localization in unstimulated transfected cells, indicating that the nuclear localization sequence is the dominant signal at steady state. However, protein kinase-C activation or mutagenesis to mimic protein kinase-C phosphorylation at a site proximal to the C-terminal nuclear localization/export sequences shifts the targeting activity of the C-terminal domain toward nuclear exclusion, indicating that the nuclear export sequence becomes the dominant signal in activated cells. Mapping of these sequences within the three-dimensional structure of the C-terminal domain indicates that their activities may be coregulated by phosphorylation and/or conformational changes in the domain. The data are consistent with a model in which intimate positioning of the nuclear localization sequence, export sequence, and phosphorylation site within a single domain provides a switch mechanism to rapidly and efficiently balance the reciprocal import and export signals in response to cellular stimuli.
Original languageEnglish
Pages (from-to)12053 - 12061
Number of pages9
Issue number43
Publication statusPublished - 2007

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