Dynein/Sunday driver mediate disorders of dynamic profiles of Golgi outposts induced by amyloid precursor protein

Dendritic abnormality is the pathological hallmark of Alzheimer’s disease (AD), but its underlying mechanism remains elusive. Here we showed that amyloid precursor protein (APP), the precursor of β-amyloid, caused dendritic defects in dendritic arborization neurons of Drosophila accompanied by Golgi outposts (GOPs) disorders. Half of the dendritic APP co-localized with GOPs, impairing their distribution and compartmental organization; in particular, the dynamic behaviors. By analyzing the state of anterograde/retrograde movements, we found that the motor protein dynein and its adapter protein Sunday driver (Syd) mediated APP-induced dynamic alterations of multi-compartment GOPs (mcGOPs) rather than single-compartment GOPs (scGOPs). Moreover, the loss of Syd rescued the defects of dendritic complexity caused by APP. Our findings indicate that APP resident in GOPs disrupts the equilibrium of anterograde/retrograde movements of mcGOPs maintained by dynein/Syd complex, resulting in dendritic abnormalities. This offers new insight into dendritic pathology in AD.