Signaling through Gsα is required for the growth and function of neuromuscular synapses in Drosophila

Abstract

Although synapses are assembled in a highly regulated fashion, synapses once formed are not static structures but continue to expand and retract throughout the life of an organism. One second messenger that has been demonstrated to play a critical role in synaptic growth and function is cAMP. Here, we have tested the idea that signaling through the heterotrimeric G protein, Gs, plays a coincident role with increases in intracellular Ca +2 in the regulation of adenylyl cyclases (ACs) during synaptic growth and in the function of synapses. In larvae containing a hypomorphic mutation in the dgs gene encoding the Drosophila Gsα protein, there is a significant decrease in the number of synaptic boutons and extent of synaptic arborization, as well as defects in the facilitation of synaptic transmission. Microscopic analysis confirmed that Gsα is localized at synapses both pre- and postsynaptically. Restricted expression of wild-type Gsα either pre- or postsynaptically rescued the mutational defects in bouton formation and defects in the facilitation of synaptic transmission, indicating that pathways activated by Gsα are likely to be involved in the reciprocal interactions between pre- and postsynaptic cells required for the development of mature synapses. In addition, this Gsα mutation interacted with fasII, dnc, and hyperexcitability mutants in a manner that revealed a coincident role for Gsα in the regulation of cAMP and FASII levels required during growth of these synapses. Our results demonstrate that Gsα-dependent signaling plays a role in the dynamic cellular reorganization that underlies synaptic growth.