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 sunday driver (syd) and the axonal transport motor kinesin-1 cause similar phenotypes in Drosophila, including aberrant accumulations of axonal cargoes. GFP-tagged mammalian SYD localizes to tubulovesicular structures that costain for kinesin-1 and a marker of the secretory pathway. Coimmunoprecipitation analysis indicates that mouse SYD forms a complex with kinesin-1 in vivo. Yeast two-hybrid analysis and in vitro interaction studies reveal that SYD directly binds kinesin-1 via the tetratricopeptide repeat (TPR) domain of 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 interacting directly with KLC.