QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 8, 3204-3213, August 2007

This Article Full Text Full Text (PDF) All Versions of this Article: E07-01-0030v1 E07-01-0030v2 18/8/3204    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moseley, G. W. Articles by Jans, D. A. Search for Related Content PubMed PubMed Citation Articles by Moseley, G. W. Articles by Jans, D. A.

Dynein Light Chain Association Sequences Can Facilitate Nuclear Protein Import

Gregory W. Moseley^*, Daniela Martino Roth^*,, Michelle A. DeJesus^*, Denisse L. Leyton^*, Richard P. Filmer^*, Colin W. Pouton, and David A. Jans^*

*Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Monash, Victoria 3800, Australia; and Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Parkville, Victoria 3052, Australia

Submitted January 16, 2007; Revised April 19, 2007; Accepted June 1, 2007
Monitoring Editor: Karsten Weis

Nuclear localization sequence (NLS)-dependent nuclear protein import is not conventionally held to require interaction with microtubules (MTs) or components of the MT motor, dynein. Here we report for the first time the role of sequences conferring association with dynein light chains (DLCs) in NLS-dependent nuclear accumulation of the rabies virus P-protein. We find that P-protein nuclear accumulation is significantly enhanced by its dynein light chain association sequence (DLC-AS), dependent on MT integrity and association with DLCs, and that P-protein-DLC complexes can associate with MT cytoskeletal structures. We also find that P-protein DLC-AS, as well as analogous sequences from other proteins, acts as an independent module that can confer enhancement of nuclear accumulation to proteins carrying the P-protein NLS, as well as several heterologous NLSs. Photobleaching experiments in live cells demonstrate that the MT-dependent enhancement of NLS-mediated nuclear accumulation by the P-protein DLC-AS involves an increased rate of nuclear import. This is the first report of DLC-AS enhancement of NLS function, identifying a novel mechanism regulating nuclear transport with relevance to viral and cellular protein biology. Importantly, this data indicates that DLC-ASs represent versatile modules to enhance nuclear delivery with potential therapeutic application.

Address correspondence to: David A. Jans (david.jans{at}med.monash.edu.au).