title: The Notch ligand E3 ligase, Mind Bomb1, regulates glutamate receptor localization in Drosophila.
abstract: The postsynaptic density (PSD) is a protein-rich network important for the localization of postsynaptic glutamate receptors (GluRs) and for signaling downstream of these receptors. Although hundreds of PSD proteins have been identified, many are functionally uncharacterized. We conducted a reverse genetic screen for mutations that affected GluR localization using Drosophila genes that encode homologs of mammalian PSD proteins. 42.8% of the mutants analyzed exhibited a significant change in GluR localization at the third instar larval neuromuscular junction (NMJ), a model synapse that expresses homologs of AMPA receptors. We identified the E3 ubiquitin ligase, Mib1, which promotes Notch signaling, as a regulator of synaptic GluR localization. Mib1 positively regulates the localization of the GluR subunits GluRIIA, GluRIIB, and GluRIIC. Mutations in mib1 and ubiquitous expression of Mib1 that lacks its ubiquitin ligase activity result in the loss of synaptic GluRIIA-containing receptors. In contrast, overexpression of Mib1 in all tissues increases postsynaptic levels of GluRIIA. Cellular levels of Mib1 are also important for the structure of the presynaptic motor neuron. While deficient Mib1 signaling leads to overgrowth of the NMJ, ubiquitous overexpression of Mib1 results in a reduction in the number of presynaptic motor neuron boutons and branches. These synaptic changes may be secondary to attenuated glutamate release from the presynaptic motor neuron in mib1 mutants as mib1 mutants exhibit significant reductions in the vesicle-associated protein cysteine string protein and in the frequency of spontaneous neurotransmission.
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Morgan
authors.initials: M
authors.lastname: Sturgeon
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Dustin
authors.initials: D
authors.lastname: Davis
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Albers
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Beatty
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Rik
authors.initials: R
authors.lastname: Austin
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Matt
authors.initials: M
authors.lastname: Ferguson
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States.
authors.forename: Brittany
authors.initials: B
authors.lastname: Tounsel
authors.affiliation: Department of Biological Sciences, Southern Illinois University Edwardsville, Edwardsville, IL 62026, United States. Electronic address: fliebl@siue.edu.
authors.forename: Faith L W
authors.initials: FL
authors.lastname: Liebl
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D017470:Receptors, Glutamate; C502570:Mib1 protein, Drosophila; D044767:Ubiquitin-Protein Ligases
keywords: Drosophila neuromuscular junction; Glutamate receptors; Postsynaptic density; Synapse; Synaptic transmission