Tae Hee Hana, Poorva Dharkarb, Mark L. Mayerb,1, and Mihaela Serpea,1
aProgram in Cellular Regulation and Metabolism and
bLaboratory of Cellular and Molecular Neurophysiology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
Abstract
The Drosophila larval neuromuscular junction (NMJ), at which glutamate acts as the excitatory neurotransmitter, is a widely used model for genetic analysis of synapse function and development. Despite decades of study, the inability to reconstitute NMJ glutamate receptor function using heterologous expression systems has complicated the analysis of receptor function, such that it is difficult to resolve the molecular basis for compound phenotypes observed in mutant flies. We find that Drosophila Neto functions as an essential component required for the function of NMJ glutamate receptors, permitting analysis of glutamate receptor responses in Xenopus oocytes. In combination with a crystallographic analysis of the GluRIIB ligand binding domain, we use this system to characterize the subunit dependence of assembly, channel block, and ligand selectivity for Drosophila NMJ glutamate receptors.
Drosophila, NMJ, Neto, glutamate receptors, crystallography
1To whom correspondence may be addressed. Email: mayerm@mail.nih.gov or mihaela.serpe@nih.gov.
Author contributions: M.L.M. and M.S. designed research; T.H.H., P.D., M.L.M., and M.S. performed research; T.H.H., P.D., M.L.M., and M.S. analyzed data; and M.L.M. and M.S. wrote the paper.