Drosophila Neto is essential for clustering glutamate receptors at the neuromuscular junction
- 1Program in Cellular Regulation and Metabolism, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Department of Zoology, University of Oklahoma, Norman, Oklahoma 73019, USA
Abstract
Neurotransmitter receptor recruitment at postsynaptic specializations is key in synaptogenesis, since this step confers functionality to the nascent synapse. The Drosophila neuromuscular junction (NMJ) is a glutamatergic synapse, similar in composition and function to mammalian central synapses. Various mechanisms regulating the extent of postsynaptic ionotropic glutamate receptor (iGluR) clustering have been described, but none are known to be essential for the initial localization and clustering of iGluRs at postsynaptic densities (PSDs). We identified and characterized the Drosophila neto (neuropilin and tolloid-like) as an essential gene required for clustering of iGluRs at the NMJ. Neto colocalizes with the iGluRs at the PSDs in puncta juxtaposing the active zones. neto loss-of-function phenotypes parallel the loss-of-function defects described for iGluRs. The defects in neto mutants are effectively rescued by muscle-specific expression of neto transgenes. Neto clustering at the Drosophila NMJ coincides with and is dependent on iGluRs. Our studies reveal that Drosophila Neto is a novel, essential component of the iGluR complexes and is required for iGluR clustering, organization of PSDs, and synapse functionality.
Keywords
- glutamatergic synapses
- postsynaptic density
- glutamate receptor
- synapse assembly
- auxiliary subunits
- Drosophila
- neuromuscular junction
Footnotes
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↵3 Corresponding author.
E-mail serpemih{at}mail.nih.gov.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.185165.111.
- Received December 16, 2011.
- Accepted March 22, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press