Molecular basis of glutamate receptor field formation

University Of Illinois At Chicago, Chicago IL

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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]