title: Akt regulates glutamate receptor trafficking and postsynaptic membrane elaboration at the Drosophila neuromuscular junction.
abstract: The Akt family of serine-threonine kinases integrates a myriad of signals governing cell proliferation, apoptosis, glucose metabolism, and cytoskeletal organization. Akt affects neuronal morphology and function, influencing dendrite growth and the expression of ion channels. Akt is also an integral element of PI3Kinase-target of rapamycin (TOR)-Rheb signaling, a pathway that affects synapse assembly in both vertebrates and Drosophila. 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). Therefore, we examined the role of Akt in the assembly and physiological function of the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse that displays developmental and activity-dependent plasticity. 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, 16802.
authors.forename: Hyun-Gwan
authors.initials: HG
authors.lastname: Lee
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Bridget K
authors.initials: BK
authors.lastname: Campion
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Nguyen
authors.forename: Scott B
authors.initials: SB
authors.lastname: Selleck
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D017470:Receptors, Glutamate; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt1; Gtaxin; glutamate receptor; membrane trafficking; subsynaptic reticulum