Nuclear Localization Signals Induce Molecular Delivery along Microtubules
Hanna Salman 1, Asmahan Abu-Arish 2, Shachar Oliel 3, Abraham Loyter 3, Joseph Klafter 4, Rony Granek 5 and Michael Elbaum 6*
1 Rockefeller University
2 McMaster University
3 The Hebrew University of Jerusalem
4 Tel Aviv University
5 Ben Gurion University of the Negev
6 Weizmann Institute of Science
* To whom correspondence should be addressed. E-mail: michael.elbaum{at}weizmann.ac.il.
Submitted on January 27, 2005
Revised on March 9, 2005
Accepted on 15 June 2005
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Abstract |
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Many essential processes in eukaryotic cells depend on regulated molecular exchange between its two major compartments, the cytoplasm and the nucleus. In general, nuclear import of macromolecular complexes is dependent on specific peptide signals and their recognition by receptors that mediate translocation through the nuclear pores. Here we address the question of how protein products bearing such nuclear localization signals (NLS) arrive at the nuclear membrane prior to import, i.e. by simple diffusion or perhaps with assistance of cytoskeletal elements or cytoskeleton-associated motor proteins. Using direct single-particle tracking and detailed statistical analysis, we show that the presence of NLS invokes active transport along microtubules in a cell-free Xenopus egg extract. Chemical and antibody inhibition of minus-end directed cytoplasmic dynein blocks this active movement. In the intact cell, where microtubules project radially from the centrosome, such an interaction would effectively deliver nuclear-targeted cargo to the nuclear envelope in preparation for import.
Key Words:
cytoskeleton, dynein, microtubules, nuclear transport, random velocity field
