Florida Atlantic University
Department of Biological Sciences
One of the pathological hallmarks of Alzheimer’s Disease (AD) is the presence of β-amyloid plaques that result from abnormal processing of the Amyloid Precursor Protein (APP). Although a great deal is known about AD pathology, relatively little is known about the normal biological function of APP. Here, we characterize the in vivo role of the Drosophila homologue (Appl) in an adult central nervous system neuron with respect to axonal transport using live imaging and immunohistochemistry.
We find that in the adult neuron full-lenth Appl is retrogradly transported and that its loss of function selectively disrupts retrograde transport of vesicles containing particular cargos. These phenotypes can be rescued with cell autonomous expression of wild type Appl, Appl lacking its cleavage domain (Appl.SD) as well as Human APP, demonstrating a conserved function for full length APP. We used Appl domain structure-function analysis to characterize the role of Appl in axonal transport of these cargo vesicles. We find that that Appl has multiple roles in cargo trafficking, during cargo sorting as well as during axonal transport. In summary, our studies provide insights into a novel endogenous Appl function in regulating retrograde trafficking, which is of potential relevance to neurodevelopment and neurodegeneration.