Physical and genetic interaction of kinesin heavy chain with Ena and Abl. M.E. Martin, J.R. Bader, A.D. Pilling, W.M. Saxton. Biology, Indiana University, Bloomington, IN.

   Microtubule-based motor proteins are critical for many cellular processes. Although a number of microtubule-based motors have been identified in axons, little is known about the regulation of these motors. To identify genes involved in axonal transport, we screened the Drosophila genome for enhancers of kinesin I-based axonal transport defects in 3rd Instar larvae. Deficiencies that removed the gene encoding Ableson tyrosine kinase (Abl) acted as dominant enhancers of kinesin heavy chain (Khc) null mutations. Yeast two-hybrid and immunoprecipitation tests showed that Enabled (Ena), an Abl substrate, interacts physically with KHC. Mutations in ena suppress the axonal transport defects caused by the Abl-Khc interaction. Together these results suggest that Ena, under the control of Abl, could be a direct negative regulator of kinesin. To test this hypothesis, we are currently imaging, tracking, and analyzing the movements of GFP-labeled organelles in axons of larvae that are mutant for Khc, Abl, and ena in various combinations. If Abl and Ena contribute directly to the control of kinesin I, we should see altered organelle distributions and/or movements in the mutant axons.