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Originally published as MBC in Press, 10.1091/mbc.E07-03-0261 on November 7, 2007

Vol. 19, Issue 1, 274-283, January 2008

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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; and {dagger}Research Institute of Molecular Pathology, 1030 Vienna, Austria

Submitted March 20, 2007; Revised September 25, 2007; Accepted October 29, 2007
Monitoring Editor: Adam Linstedt

A screen for genes required in Drosophila eye development identified an 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 green fluorescent protein-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 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.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-03-0261) on November 7, 2007.

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

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




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