Drosophila Neto is Essential for Clustering Glutamate Receptors at the Neuromuscular Junction
Overview
Affiliations
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.
The gating properties of Drosophila NMJ glutamate receptors and their dependence on Neto.
Han T, Vicidomini R, Ramos C, Mayer M, Serpe M J Physiol. 2024; 602(24):7043-7064.
PMID: 39602131 PMC: 11649521. DOI: 10.1113/JP287331.
Neto proteins differentially modulate the gating properties of NMJ glutamate receptors.
Han T, Vicidomini R, Ramos C, Mayer M, Serpe M bioRxiv. 2024; .
PMID: 38903091 PMC: 11188076. DOI: 10.1101/2024.04.22.590603.
Excess glutamate release triggers subunit-specific homeostatic receptor scaling.
Han Y, Goel P, Chen J, Perry S, Tran N, Nishimura S Cell Rep. 2023; 42(7):112775.
PMID: 37436892 PMC: 10529671. DOI: 10.1016/j.celrep.2023.112775.
Rapid homeostatic modulation of transsynaptic nanocolumn rings.
Muttathukunnel P, Frei P, Perry S, Dickman D, Muller M Proc Natl Acad Sci U S A. 2022; 119(45):e2119044119.
PMID: 36322725 PMC: 9659372. DOI: 10.1073/pnas.2119044119.
Local BMP signaling: A sensor for synaptic activity that balances synapse growth and function.
Vicidomini R, Serpe M Curr Top Dev Biol. 2022; 150:211-254.
PMID: 35817503 PMC: 11102767. DOI: 10.1016/bs.ctdb.2022.04.001.