Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the Drosophila neuromuscular junction.
Bottom Line: The single Drosophila Akt family member, Akt1 selectively altered the postsynaptic targeting of one glutamate receptor subunit, GluRIIA, and was required for the expansion of a specialized postsynaptic membrane compartment, the subsynaptic reticulum (SSR).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: Based on the similar ultrastructural changes in the SSR and muscle membrane organization resulting from reductions in Gtaxin and Akt1 function, Gtaxin was a logical candidate as a downstream target of Akt1 activity. To explore this possibility, we examined Gtaxin levels and distribution in animals with muscle-specific expression of Akt1RNAi (Mef2-GAL4>UAS-Akt1RNAi) or a constitutively active form of Akt1 (Mef2-GAL4>UAS-Akt1CA). In wild-type animals, Gtaxin immunoreactivity is concentrated at the SSR [Fig. 6(B,C)], and muscle-directed RNAi of Akt1 greatly reduced Gtaxin levels at this postsynaptic specialization [Fig. 6(F,G)]. Gtaxin has been implicated in SSR formation not only on account of the reduction of SSR complexity in Gtaxin mutant but also from the production of ectopic, mCD8-GFP labeled membranous structures in animals overexpressing wild-type Gtaxin (Gorczyca et al., 2007). Muscle-directed expression of Akt1CA produced membranous structures with the same visible features. In these animals, Gtaxin was present at increased levels and localized to patches throughout the muscle [Fig. 6(I–K)]. These ectopic membrane elaborations were confirmed at the TEM level and are structurally similar to those documented in animals overexpressing Gtaxin in the muscle [Fig. 6(M–O)].
Affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.