The role of Akt in neural muscular junction development.

Abstract

In this study we used the well studied model organism, Drosophila melanogaster, to gain further insight into the components involved in synaptogenesis. Using the vast array of techniques available to the Drosophila geneticist we examined the roles of several well known components of growth regulatory pathways in synaptogenesis at the Drosophila NMJ. Employing both immunoflourescence and electrophysiology we were able to gain insight into changes in both the structure and the function of the NMJ.Synaptic development, as well as axon pathfinding and phototaxis are modified when the growth regulatory pathway TSC/Rheb/Tor is upregulated via overexpression of Rheb. However, we find that although axon defects and phototaxis deficits are rescued by modifications in nutritional inputs to this pathway, Rheb mediated synaptic enhancements remain unaltered. The kinase Akt is a shared substrate between the TSC/Rheb/Tor and the PI3 kinase insulin sensing pathway, which shows a comparable synaptic phenotype when overactivated. We therefore, hypothesized that loss of Akt would result in a decrease in synapse size and function. In contrast to our hypothesis we find that Akt is a negative regulator of synaptogenesis. Akt contributes to both pre and postsynaptic events. Akt mediates muscle size, synaptic area and GluR subunit levels and localization. Loss of Akt also results in changes in the levels of Dorsal and its binding partner Cactus, as well as in the levels of the SSR associated proteins Syndapin and Dlg.