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Title: Functional reconstitution of Drosophila melanogaster NMJ glutamate receptors

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [2];  [1]
  1. National Inst. of Health, Bethesda, MD (United States). The Eunice Kennedy Shriver National Inst. of Child Health and Human Development. Program in Cellular Regulation and Metabolism
  2. National Inst. of Health, Bethesda, MD (United States). The Eunice Kennedy Shriver National Inst. of Child Health and Human Development. Lab. of Cellular and Molecular Neurophysiology

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. In this paper, 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. Finally, 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.

Research Organization:
National Inst. of Health, Bethesda, MD (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)
Grant/Contract Number:
W-31-109-Eng-38
OSTI ID:
1182323
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 19; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 33 works
Citation information provided by
Web of Science

References (46)

Glutamate Receptor Ion Channels: Structure, Regulation, and Function journal August 2010
L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction. journal October 1976
The effect on crayfish muscle of iontophoretically applied glutamate journal March 1964
Reconstitution of invertebrate glutamate receptor function depends on stargazin-like proteins journal July 2006
A modern ionotropic glutamate receptor with a K+ selectivity signature sequence journal March 2011
Glutamate Receptor Expression Regulates Quantal Size and Quantal Content at the Drosophila Neuromuscular Junction journal April 1999
Differential Localization of Glutamate Receptor Subunits at the Drosophila Neuromuscular Junction journal February 2004
An Essential Drosophila Glutamate Receptor Subunit That Functions in Both Central Neuropil and Neuromuscular Junction journal March 2005
Four Different Subunits Are Essential for Expressing the Synaptic Glutamate Receptor at Neuromuscular Junctions of Drosophila journal March 2005
Gating Characteristics Control Glutamate Receptor Distribution and Trafficking In Vivo journal September 2014
Drosophila Neto is essential for clustering glutamate receptors at the neuromuscular junction journal April 2012
A Transmembrane Accessory Subunit that Modulates Kainate-Type Glutamate Receptors journal February 2009
The SOL-2/Neto Auxiliary Protein Modulates the Function of AMPA-Subtype Ionotropic Glutamate Receptors journal September 2012
SOL-1 is a CUB-domain protein required for GLR-1 glutamate receptor function in C. elegans journal January 2004
Desensitization and resensitization kinetics of glutamate receptor channels from Drosophila larval muscle journal May 1997
Concanavalin A blocks desensitisation of glutamate receptors on insect muscle fibres journal February 1976
Anions Mediate Ligand Binding in Adineta vaga Glutamate Receptor Ion Channels journal March 2013
Activation kinetics of Glutamate receptor channels from wild-type Drosophila muscle journal October 1996
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels journal October 1991
RNA editing of AMPA receptor subunit GluR-B: A base-paired intron-exon structure determines position and efficiency journal December 1993
Determinants of ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: Diversity by RNA editing journal March 1993
X-ray structure, symmetry and mechanism of an AMPA-subtype glutamate receptor journal November 2009
Structure and Dynamics of AMPA Receptor GluA2 in Resting, Pre-Open, and Desensitized States journal August 2014
Crystal structure of a heterotetrameric NMDA receptor ion channel journal May 2014
NMDA receptor structures reveal subunit arrangement and pore architecture journal June 2014
Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block journal August 1995
Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors. journal July 1995
Argiotoxin detects molecular differences in AMPA receptor channels journal June 1993
Two calcium-activated chloride conductances in Xenopus laevis oocytes permeabilized with the ionophore A23187. journal January 1989
Expression Cloning of TMEM16A as a Calcium-Activated Chloride Channel Subunit journal September 2008
Amino acid substitutions in the pore of rat glutamate receptors at sites influencing block by polyamines journal October 1999
Identification of a site in glutamate receptor subunits that controls calcium permeability journal August 1991
Structural determinants of ion flow through recombinant glutamate receptor channels journal June 1991
Permeation and block of rat glur6 glutamate receptor channels by internal and external polyamines journal August 1997
Excitatory Amino Acid Transmitters journal April 1981
Crystal Structures of the GluR5 and GluR6 Ligand Binding Cores: Molecular Mechanisms Underlying Kainate Receptor Selectivity journal February 2005
Mechanism of Activation and Selectivity in a Ligand-Gated Ion Channel:  Structural and Functional Studies of GluR2 and Quisqualate , journal December 2002
Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface journal November 2012
Structure and Assembly Mechanism for Heteromeric Kainate Receptors journal July 2011
Building a synapse: A complex matter journal July 2013
Development of the embryonic neuromuscular synapse of Drosophila melanogaster journal January 1993
Junctional and extrajunctional glutamate receptor channels in Drosophila embryos and larvae journal December 1995
Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. journal December 1987
Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit journal January 1992
Control of human potassium channel inactivation by editing of a small mRNA hairpin journal September 2004
Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila journal September 2013

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Glutamatergic Synthesis, Recycling, and Receptor Pharmacology at Drosophila and Crustacean Neuromuscular Junctions book September 2017
Genome-Wide Association Study of Circadian Behavior in Drosophila melanogaster journal October 2018
Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release and homeostatic plasticity journal January 2019
Homeostatic plasticity can be induced and expressed to restore synaptic strength at neuromuscular junctions undergoing ALS-related degeneration journal July 2017
A screen for genes that regulate synaptic growth reveals mechanisms that stabilize synaptic strength posted_content September 2018
Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction posted_content October 2019
Presynaptic depression maintains stable synaptic strength in developmentally arrested Drosophila larvae preprint November 2019
Glutamate signaling at cytoneme synapses journal February 2019
Intellectual disability and autism spectrum disorders ‘on the fly’: insights from Drosophila journal May 2019
Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation journal April 2018
Neto-α Controls Synapse Organization and Homeostasis at the Drosophila Neuromuscular Junction journal July 2020
What does it take to get the job done? journal November 2015
A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction journal January 2016
Tenectin recruits integrin to stabilize bouton architecture and regulate vesicle release at the Drosophila neuromuscular junction journal June 2018