The kinesin-associated protein UNC-76 is required for axonal transport in the Drosophila nervous system.
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 Czeta, and the role of FEZ1 in axon outgrowth, we propose that UNC-76 helps integrate kinesin activity in response to transport requirements in axons.
Gindhart
Joseph G
JG
Biology Department, University of Massachusetts, Boston, Massachusetts 02125, USA. joseph.gindhart@umb.edu
Chen
Jinyun
J
Faulkner
Melissa
M
Gandhi
Rita
R
Doerner
Karl
K
Wisniewski
Tiffany
T
Nandlestadt
Aline
A
D000595:Amino Acid Sequence; D000818:Animals; D001370:Axonal Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion; D008264:Macrophages; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017421:Sequence Analysis; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; C484031:UNC-76 protein, Drosophila; D016547:Kinesins