Molecular basis of glutamate receptor field formation

Summary

Principal Investigator: David E Featherstone
Abstract: [unreadable] DESCRIPTION (provided by applicant): Excitatory signaling in the central nervous system occurs primarily via glutamate receptors. A molecular understanding of the development, maintenance, and modulation of postsynaptic glutamate receptor fields is therefore very important. However, the molecular mechanisms underlying glutamate receptor field formation are incompletely understood. We are addressing this problem by identifying genes and mechanisms involved in glutamate receptor field formation using a genetic approach in Drosophila. We have isolated several allelic mutations that result in complete and specific loss of postsynaptic glutamate receptor fields. We will identify and clone the mutant gene (which we named 'bad reception', abbreviated 'brec'), then determine the expression and localization of both the brec gene and protein [aim 1]. Properly localized postsynaptic glutamate receptor fields do not form unless the postsynaptic cell is first contacted by the presynaptic cell. After presynaptic contact, glutamate receptor field function increases several hundred-fold within minutes. The molecular mechanisms underlying this process are unknown. To determine whether brec or similar proteins could be involved in this process, we will test whether the initial induction of glutamate receptor fields requires transcription of new receptor subunit genes, or primarily involves translation of pre-existing, possibly pre-localized, receptor subunit mRNAs [aim 2]. To help understand the function of brec and similar proteins in vivo, we will generate and utilize glutamate receptor subunit transgenes tagged with green fluorescent protein (GFP) [aim 3]. Finally, we will continue our forward genetic search for new genes involved in the development of postsynaptic glutamate receptor fields [aim 4] using the new tools and knowledge generated in aims 1-3. The proteins and mechanisms identified in this study (including brec) represent potential drug targets that could be important for understanding and treating neurological conditions such as epilepsy, schizophrenia, damage due to stroke, learning disorders, spinal cord regeneration, or drug addiction [unreadable] [unreadable]
Funding Period: 2003-02-01 - 2009-01-31
more information: NIH RePORT

Top Publications

  1. ncbi Hemolymph amino acid variations following behavioral and genetic changes in individual Drosophila larvae
    Sujeewa C Piyankarage
    Department of Chemistry MC 111, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    Amino Acids 38:779-88. 2010
  2. pmc Discs-large (DLG) is clustered by presynaptic innervation and regulates postsynaptic glutamate receptor subunit composition in Drosophila
    Kaiyun Chen
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
    BMC Biol 3:1. 2005
  3. pmc Effect of ambient extracellular glutamate on Drosophila glutamate receptor trafficking and function
    Kaiyun Chen
    Department of Biological Sciences, University of Illinois at Chicago, 840 W Taylor Street MC 067, Chicago, IL 60607, USA
    J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195:21-9. 2009
  4. pmc Hemolymph amino acid analysis of individual Drosophila larvae
    Sujeewa C Piyankarage
    Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    Anal Chem 80:1201-7. 2008
  5. pmc A glial amino-acid transporter controls synapse strength and courtship in Drosophila
    Yael Grosjean
    Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA
    Nat Neurosci 11:54-61. 2008
  6. pmc Derailed regulates development of the Drosophila neuromuscular junction
    Faith L W Liebl
    Cell and Developmental Biology Program, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Dev Neurobiol 68:152-65. 2008
  7. pmc Regulation of synaptic transmission by ambient extracellular glutamate
    David E Featherstone
    Department of Biological Sciences, University of Illinois at Chicago 60607, USA
    Neuroscientist 14:171-81. 2008
  8. pmc Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo
    Hrvoje Augustin
    Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurosci 27:111-23. 2007
  9. pmc Genome-wide P-element screen for Drosophila synaptogenesis mutants
    Faith L W Liebl
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurobiol 66:332-47. 2006
  10. pmc A single vesicular glutamate transporter is sufficient to fill a synaptic vesicle
    Richard W Daniels
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Neuron 49:11-6. 2006

Scientific Experts

  • Kaiyun Chen
  • David E Featherstone
  • Faith L W Liebl
  • Hrvoje Augustin
  • Sujeewa C Piyankarage
  • Yael Grosjean
  • Julie Karr
  • Scott A Shippy
  • Richard W Daniels
  • Subhashree Ganesan
  • Vasia Vagin
  • Oxana Olenkina
  • Vladimir Gvozdev
  • Jean Fran├žois Ferveur
  • Micheline Grillet
  • Qi Sheng
  • Catherine A Collins
  • Aaron DiAntonio
  • Maria V Gelfand

Detail Information

Publications15

  1. ncbi Hemolymph amino acid variations following behavioral and genetic changes in individual Drosophila larvae
    Sujeewa C Piyankarage
    Department of Chemistry MC 111, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    Amino Acids 38:779-88. 2010
    ..Hemolymph amino acid analyses of stressed larvae of two control and two mutant genotypes indicated that behavior-related hemolymph chemical changes are also genotype dependent...
  2. pmc Discs-large (DLG) is clustered by presynaptic innervation and regulates postsynaptic glutamate receptor subunit composition in Drosophila
    Kaiyun Chen
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
    BMC Biol 3:1. 2005
    ....
  3. pmc Effect of ambient extracellular glutamate on Drosophila glutamate receptor trafficking and function
    Kaiyun Chen
    Department of Biological Sciences, University of Illinois at Chicago, 840 W Taylor Street MC 067, Chicago, IL 60607, USA
    J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195:21-9. 2009
    ..Results suggest that glutamate receptor protein is redistributed, but not degraded, after prolonged exposure to high extracellular glutamate...
  4. pmc Hemolymph amino acid analysis of individual Drosophila larvae
    Sujeewa C Piyankarage
    Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
    Anal Chem 80:1201-7. 2008
    ....
  5. pmc A glial amino-acid transporter controls synapse strength and courtship in Drosophila
    Yael Grosjean
    Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA
    Nat Neurosci 11:54-61. 2008
    ....
  6. pmc Derailed regulates development of the Drosophila neuromuscular junction
    Faith L W Liebl
    Cell and Developmental Biology Program, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Dev Neurobiol 68:152-65. 2008
    ..Our findings reveal a novel signaling mechanism that regulates morphology of the Drosophila NMJ...
  7. pmc Regulation of synaptic transmission by ambient extracellular glutamate
    David E Featherstone
    Department of Biological Sciences, University of Illinois at Chicago 60607, USA
    Neuroscientist 14:171-81. 2008
    ..Unfortunately, the mechanisms regulating ambient extracellular glutamate and glutamate receptor desensitization remain poorly understood and understudied...
  8. pmc Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo
    Hrvoje Augustin
    Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurosci 27:111-23. 2007
    ....
  9. pmc Genome-wide P-element screen for Drosophila synaptogenesis mutants
    Faith L W Liebl
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurobiol 66:332-47. 2006
    ....
  10. pmc A single vesicular glutamate transporter is sufficient to fill a synaptic vesicle
    Richard W Daniels
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Neuron 49:11-6. 2006
    ..Consistent with the presence of empty vesicles, at dvglut mutant synapses synaptic vesicles are smaller, suggesting that vesicle filling and/or transporter level is an important determinant of vesicle size...
  11. pmc The 4.1 protein coracle mediates subunit-selective anchoring of Drosophila glutamate receptors to the postsynaptic actin cytoskeleton
    Kaiyun Chen
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurosci 25:6667-75. 2005
    ....
  12. pmc Genes involved in Drosophila glutamate receptor expression and localization
    Faith L W Liebl
    Dept of Cell and Structural Biology, Univ of Illinois at Urbana Champaign, Urbana, USA
    BMC Neurosci 6:44. 2005
    ..We screened transposon mutants generated by the ongoing Drosophila Gene Disruption Project in an effort to identify the different types of genes required for glutamate receptor cluster development...
  13. pmc An essential Drosophila glutamate receptor subunit that functions in both central neuropil and neuromuscular junction
    David E Featherstone
    Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA
    J Neurosci 25:3199-208. 2005
    ..These studies reveal GluRIID as a newly identified glutamate receptor subunit that is essential for glutamate receptor assembly/stabilization in the peripheral NMJ and required for properly patterned motor output in the CNS...
  14. pmc Regulation of glutamate receptor subunit availability by microRNAs
    Julie Karr
    Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
    J Cell Biol 185:685-97. 2009
    ....