Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the Drosophila neuromuscular junction.
Bottom Line: Our recent findings demonstrated that disruption of this pathway in Drosophila is responsible for a number of neurodevelopmental deficits that may also affect phenotypes associated with tuberous sclerosis complex, a disorder resulting from mutations compromising the TSC1/TSC2 complex, an inhibitor of TOR (Dimitroff et al., 2012).Several lines of evidence indicated that Akt1 influences SSR assembly by regulation of Gtaxin, a Drosophila t-SNARE protein (Gorczyca et al., 2007) in a manner independent of the mislocalization of GluRIIA.Our findings show that Akt1 governs two critical elements of synapse development, neurotransmitter receptor localization, and postsynaptic membrane elaboration.
Affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.Show MeSH
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Mentions: Akt1 plays a central role in a number of signaling processes, acting both downstream and upstream of growth factor and target of rapamycin-directed events. The Akt1 kinase governs a number of cellular activities including cell proliferation, cell survival, and cytoskeleton organization [Fig. 1(A)]. Given these diverse and critical functions, we explored the role of Akt1 in synapse assembly. In addition to the well-described Akt1 mutant alleles (Staveley et al., 1998; Mozden and Rubin, 1999; Guo and Zhong, 2006), we used an Akt1RNAi transgene (Dietzl et al., 2007) to inhibit Akt1 function selectively in either motoneurons or muscle cells. To assess the level of inhibition achieved by the Akt1RNAi construct, we measured the level of phosphorylated Akt1 (active form of Akt1) by western blot. Using a muscle-directed GAL4 to drive the expression of UAS-Akt1RNAi, phosphorylated Akt1 protein was reduced to 24.2% of wild-type level in third instar larval muscle tissue [Fig. 1(B)].
Affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.