Kinesin-dependent axonal transport is mediated by the Sunday driver (SYD) protein

A broadly conserved membrane-associated protein required for the functional interaction of kinesin-1 with axonal cargo was identified. Mutations in su nday driver (syd) and the axonal transport motor kinesin-1 cause similar ph enotypes in Drosophila, including aberrant accumulations of axonal cargoes. GFP-tagged mammalian SYD localizes to tubulovesicular structures that cost ain for kinesin-1 and a marker of the secretory pathway. Coimmunoprecipitat ion analysis indicates that mouse SYD forms a complex with kinesin-1 in viv o. Yeast two-hybrid analysis and in vitro interaction studies reveal that S YD directly binds kinesin-1 via the tetratricopeptide repeat (TPR) domain o f kinesin light chain (KLC) with K-d approximate to 200 nM. We propose that SYD mediates the axonal transport of at least one class of vesicles by int eracting directly with KLC.