The armadillo protein p0071 controls directionality of kinesin-2 driven transport by mediating KIF3 motor complex stability

Abstract

In this study, a novel and unexpected role of the armadillo repeat protein p0071 in cellular transport is described. P0071 abrogation in cultured cells significantly interferes with secretion of various secretory cargo proteins. This effect is specifically targeting cargo substrates of the microtubule based heterotrimeric kinesin-2 complex, which comprises of KIF3A, KIF3B and KAP3. Impairment of both p0071 and KIF3B leads to aberrant movement of chromogranin A granules in neuroendocrine tumor cells due to impaired directional persistence of vesicle transport. This effect is likely explained by a potential function of p0071 as a stabilizing linker within the kinesin-2 complex since it could be shown that p0071 mediates the interaction between the motor subunit KIF3B and the cargo-adaptor subunit, KAP3.