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: We began assessing the role of Akt1 in NMJ assembly by examining the distribution and level of glutamate receptor IIA (GluRIIA), one of the neurotransmitter receptor subunits at this glutaminergic synapse. Glutamate is the major excitatory neurotransmitter at the type I bouton of the Drosophila larval NMJ (Brunner and Okane, 1997; Collins and DiAntonio, 2007). The NMJ glutamate receptor (GluR) is a heterotetramer comprised of three invariant subunits: GluRIIC, D, and E. The fourth subunit, either GluRIIA or B, determines the type and the electrophysiological properties of the receptor (DiAntonio et al., 1999; Featherstone et al., 2005; Qin et al., 2005a; DiAntonio, 2006). Subunit GluRIIA and B competitively bind to GluRIIC; hence, the preferential expression of these two subunits constitutes one element of developmental plasticity exhibited by this synapse (Marrus et al., 2004). We examined the levels and distributions of GluRIIA using a well-characterized monoclonal antibody, anti-GluRIIA (Featherstone et al., 2002; Qin et al., 2005a; Karr et al., 2009). The specificity of this antibody has been well documented by showing that immunoreactive signal is lost in GluRIIA mutant (Marrus et al., 2004). Partial loss of Akt1 function, achieved with the heteroallelic combination Akt11/Akt104226, altered GluRIIA distributions and levels, with a reduction at postsynaptic structures and the appearance of GluRIIA immunoreactivity within repeated bands throughout the muscle cells [Fig. 2 compare (A), (B) to (C), (D)]. This latter phenotype was more prominent in muscles 15 and 16 and was observed to a lesser extent in muscles 6 and 7, the postsynaptic cells typically used for electrophysiological analysis [arrowheads in Fig. 2(C,D)].
Affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.