UC San Diego

This work explores two unresolved issues in neurobiology. First, we studied the fundamental question of how microtubule motors regulate their activity to achieve bi- directional transport in axons. Because good in vivo model systems and quantitative approaches were lacking, we developed an in vivo neuronal system and software to study the behavior of fluorescent vesicles. Our approach consisted of quantitative analysis of YFP-tagged amyloid precursor protein (APPYFP) axonal transport in segmental nerves of Drosophila melanogaster using heterozygous animals and a standardized imaging system. This allowed us to assess the contribution of individual motor subunits and accessory proteins to coordinated axonal transport. Our approach yielded a novel model for how motor proteins work together to achieve bi-directional transport. Second, we studied genetic manipulations hypothesized to rescue axonal transport defects induced by overexpression of APP. This research is potentially relevant to Alzheimer's disease (AD) as well as its treatment. We found that APP overexpression disrupts axonal transport, and these deficits can be partially rescued by two separate genetic manipulations. These observations suggest that certain genetic approaches may help reverse axonal transport defects induced by APP overexpression, and this may have implications for the development of novel therapeutic approaches to treat neurodegeneration