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Vol. 16, Issue 9, 4225-4230, September 2005
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* Department of Biology, Indiana University, Bloomington, IN 47405;
McArdle Laboratory, University of Wisconsin, Madison, WI 53706
Submitted February 10, 2005;
Revised June 13, 2005;
Accepted June 15, 2005
Monitoring Editor: John Pringle
Relatively little is known about how microtubule motors are controlled or about how the functions of different cytoskeletal systems are integrated. A yeast two-hybrid screen for proteins that bind to Drosophila Enabled (Ena), an actin polymerization factor that is negatively regulated by Abl tyrosine kinase, identified kinesin heavy chain (Khc), a member of the kinesin-1 subfamily of microtubule motors. Coimmunoprecipitation from Drosophila cytosol confirmed a physical interaction between Khc and Ena. Kinesin-1 motors can carry organelles and other macromolecular cargoes from neuronal cell bodies toward terminals in fast-axonal-transport. Ena distribution in larval axons was not affected by mutations in the Khc gene, suggesting that Ena is not itself a fast transport cargo of Drosophila kinesin-1. Genetic interaction tests showed that in a background sensitized by reduced Khc gene dosage, a reduction in Abl gene dosage caused distal paralysis and axonal swellings. A concomitant reduction in ena dosage rescued those defects. These results suggest that Ena/VASP, when not inhibited by the Abl pathway, can bind Khc and reduce its transport activity in axons.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
These authors contributed equally to this work.
Address correspondence to: William Saxton (bsaxton{at}bio.indiana.edu).
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