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Vol. 14, Issue 8, 3356-3365, August 2003

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The Kinesin-associated Protein UNC-76 Is Required for Axonal Transport in the Drosophila Nervous System

Joseph G. Gindhart ^* , Jinyun Chen ^*, Melissa Faulkner ^*, Rita Gandhi , Karl Doerner, Tiffany Wisniewski ^* , and Aline Nandlestadt ^*

^* Biology Department, University of Massachusetts, Boston, Massachusetts 02125; Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Submitted December 9, 2002; Revised March 31, 2003; Accepted March 31, 2003
Monitoring Editor: J. Richard McIntosh

Kinesin-I is essential for the transport of membrane-bound organelles in neural and nonneural cells. However, the means by which kinesin interacts with its intracellular cargoes, and the means by which kinesin–cargo interactions are regulated in response to cellular transport requirements are not fully understood. The C terminus of the Drosophila kinesin heavy chain (KHC) was used in a two-hybrid screen of a Drosophila cDNA library to identify proteins that bind specifically to the kinesin tail domain. UNC-76 is an evolutionarily conserved cytosolic protein that binds to the tail domain of KHC in two-hybrid and copurification assays, indicating that kinesin and UNC-76 form a stable complex in vivo. Loss of Drosophila Unc-76 function results in locomotion and axonal transport defects reminiscent of the phenotypes observed in kinesin mutants, suggesting that UNC-76 is required for kinesin-dependent axonal transport. Unc-76 exhibits dosage-sensitive genetic relationships with Khc and Kinesin light chain mutations, further supporting the hypothesis that UNC-76 and kinesin-I work in a common transport pathway. Given the interaction of FEZ1, the mammalian homolog of UNC-76, with protein kinase C, and the role of FEZ1 in axon outgrowth, we propose that UNC-76 helps integrate kinesin activity in response to transport requirements in axons.

Present address: AstraZeneca R&D Boston, 35 Gatehouse Dr., Waltham, MA 02451.

Corresponding author. E-mail address: joseph.gindhart{at}umb.edu.

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