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MBC in Press, published online ahead of print November 7, 2007
Mol. Biol. Cell 10.1091/mbc.E07-03-0261

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Submitted on March 20, 2007
Revised on September 25, 2007
Accepted on October 29, 2007

Identification of an Axonal Kinesin-3 Motor for Fast Anterograde Vesicle Transport that Facilitates Retrograde Transport of Neuropeptides

Rosemarie V. Barkus,* Olga Klyachko,* Dai Horiuchi,* Barry J. Dickson,{dagger} and William M. Saxton*{ddagger}

*Department of Biology, Indiana University, Bloomington, IN 47405-3700; {dagger}Research Institute of Molecular Pathology, 1030 Vienna, Austria

Monitoring Editor: Adam Linstedt

A screen for genes required in Drosophila eye development identified a UNC-104/Kif1 related kinesin-3 microtubule motor. Analysis of mutants suggested that Drosophila Unc-104 has neuronal functions that are distinct from those of the classic anterograde axonal motor, kinesin-1. In particular, unc-104 mutations did not cause the distal paralysis and focal axonal swellings characteristic of kinesin-1 (Khc) mutations. However, like Khc mutations, unc-104 mutations caused motoneuron terminal atrophy. The distributions and transport behaviors of GFP-tagged organelles in motor axons indicate that Unc-104 is a major contributor to the anterograde fast transport of neuropeptide-filled vesicles, that it also contributes to anterograde transport of synaptotagmin-bearing vesicles, and that it contributes little or nothing to anterograde transport of mitochondria, which are likely transported primarily by Khc. Remarkably, unc-104 mutations inhibited retrograde runs by neurosecretory vesicles but not by the other two organelles. This suggests that Unc-104, a member of an anterograde kinesin subfamily, contributes to an organelle-specific dynein-driven retrograde transport mechanism.


{ddagger}Present address: Department of MCD Biology, University of California, Santa Cruz, CA 95060.

Address correspondence to: William M. Saxton (saxton{at}biology.ucsc.edu)







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