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: The formation of mCD8-GFP-labelled membrane patches mediated by Akt1CA was also found to be dependent on Gtaxin. The ectopic membranous patches induced by Akt1CA expression in the muscle were visualized by mCD8-mRFP and showed some features of SSR, namely concentration of α-Spectrin and DLG (Pielage et al., 2006) [Fig. 7]. Reduction of Gtaxin by RNA interference blocked the Akt1CA-mediated formation of these “ectopic” SSR structures [Fig. 7(B,D)]. The ectopic membrane patches induced by Akt1CA overexpression were not reduced by expression of a control UAS-transgene, excluding the possibility that suppression of Akt1CA function was due to titration of GAL4 proteins in GtaxinRNAi expressed animals (data not shown). Inhibition of Gtaxin by GtaxinRNAi expression in muscle induced loss of mCD8 at the SSR but DLG remained at the postsynaptic specialization [Fig. 7(F,H)]. In addition, GluRIIA localization was not disrupted by GtaxinRNAi, indicating that Gtaxin does not play a role in this aspect of Akt1 function and is consistent with published findings (Gorczyca et al., 2007) [Fig. 7(J)]. These results demonstrated that Gtaxin is required for Akt1CA-mediated formation of ectopic membranous structures. It is of interest that Gtaxin bears a consensus sequence (RXRXXS/T) for Akt1 phosphorylation, indicating a potential phosphorylation site at Serine 255, suggesting that Gtaxin could be a direct target of Akt1 activity (Datta et al., 1999; Zhang et al., 2002).
Affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.