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 ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS045628-03
Application #
6847990
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Talley, Edmund M
Project Start
2003-02-01
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
3
Fiscal Year
2005
Total Cost
$326,031
Indirect Cost
Name
University of Illinois at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Ziegler, Anna B; Augustin, Hrvoje; Clark, Nathan L et al. (2016) The Amino Acid Transporter JhI-21 Coevolves with Glutamate Receptors, Impacts NMJ Physiology, and Influences Locomotor Activity in Drosophila Larvae. Sci Rep 6:19692
Manière, Gérard; Ziegler, Anna B; Geillon, Flore et al. (2016) Direct Sensing of Nutrients via a LAT1-like Transporter in Drosophila Insulin-Producing Cells. Cell Rep 17:137-148
Piyankarage, Sujeewa C; Augustin, Hrvoje; Featherstone, David E et al. (2010) Hemolymph amino acid variations following behavioral and genetic changes in individual Drosophila larvae. Amino Acids 38:779-88
Chen, Kaiyun; Augustin, Hrvoje; Featherstone, David E (2009) Effect of ambient extracellular glutamate on Drosophila glutamate receptor trafficking and function. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 195:21-9
Karr, Julie; Vagin, Vasia; Chen, Kaiyun et al. (2009) Regulation of glutamate receptor subunit availability by microRNAs. J Cell Biol 185:685-97
Featherstone, David E; Yanoga, Fatoumata; Grosjean, Yael (2008) Accelerated bang recovery in Drosophila genderblind mutants. Commun Integr Biol 1:14-17
Piyankarage, Sujeewa C; Augustin, Hrvoje; Grosjean, Yael et al. (2008) Hemolymph amino acid analysis of individual Drosophila larvae. Anal Chem 80:1201-7
Featherstone, David E; Shippy, Scott A (2008) Regulation of synaptic transmission by ambient extracellular glutamate. Neuroscientist 14:171-81
Liebl, Faith L W; Wu, Yuping; Featherstone, David E et al. (2008) Derailed regulates development of the Drosophila neuromuscular junction. Dev Neurobiol 68:152-65
Grosjean, Yael; Grillet, Micheline; Augustin, Hrvoje et al. (2008) A glial amino-acid transporter controls synapse strength and courtship in Drosophila. Nat Neurosci 11:54-61

Showing the most recent 10 out of 17 publications