A broadly conserved membrane-associated protein required for the functional interaction of kinesin-I with axonal cargo was identified. Mutations in
sunday driver (
syd) and the axonal transport motor
kinesin-I cause similar phenotypes in
Drosophila, including aberrant accumulations of axonal cargoes. GFP-tagged mammalian SYD localizes to tubulovesicular structures that costain for kinesin-I and a marker of the secretory pathway. Coimmunoprecipitation analysis indicates that mouse SYD forms a complex with kinesin-I in vivo. Yeast two-hybrid analysis and in vitro interaction studies reveal that SYD directly binds kinesin-I via the tetratricopeptide repeat (TPR) domain of kinesin light chain (KLC) with K
d ![](/images/glyphs/BQ3.GIF)
200 nM. We propose that SYD mediates the axonal transport of at least one class of vesicles by interacting directly with KLC.