Regulation of glutamate receptor transcript abundance during embryonic and larval development.

摘要

Glutamate receptors are critical for the proper function of the central nervous system, as they mediate the majority of fast excitatory neurotransmission. Critical functions of the CNS include, but are not limited to, sensory and motor processing, and learning and memory formation. In the mammalian central nervous system, glutamate is the primary excitatory neurotransmitter; it is also found to be the excitatory neurotransmitter utilized at the Drosophila neuromuscular junction (Schuster et al., 1991). This similarity allows researchers to employ Drosophila as a powerful model system for which to study these essential receptors. The body wall muscles on which these glutamatergic synapses are found are also relatively simple, easily accessible and well defined to facilitate study (Anderson et al., 1988; Halpern et al., 1991; Johansen et al., 1989). The ability to create transgenic lines, deletion mutants and knock down genes using RNA interference through the use of the UAS/Ga14 system has also proven to be an essential tool in this study (Fjose et al., 2001; Roman, 2004).;The ionotropic glutamate receptors are the primary mediators of excitatory neurotransmission in the central nervous system (Bogdanik et al., 2004). Ionotropic glutamate receptors are a well-characterized category of ligand-gated ion channels. There are three known subtypes of ionotropic glutamate receptors, AMPA, kainate, and the NMDA receptors. The primary excitatory receptors at the mammalian brain are either the AMPA or kainite subtype, the kainate subtype are also the primary receptors found at the Drosophila NMJ.;The Drosophila ionotropic glutamate receptors found at the NMJ are proposed to be heteromeric tetramer complexes formed from five different glutamate receptor subunits, GluRIIA, GluRIIB, GluRIIC (formerly GluRIII), GluRIID and GluRIIE (DiAntonio et al., 1999; Featherstone et al., 2005; Marrus et al., 2004; Petersen et al., 1997b). These receptors are either A-type or B-type. A-type receptors are composed of GluRIIA, GluRIIC, GluRIID, and GluRIIE, while B-type receptors are composed of GluRIIB, GluRIIC, GluRIID, and GluRIIE. These two receptor types possess differing properties and currents, and localization patterns within Drosophila (Chen et al., 2005; Davis et al., 1998; DiAntonio et al., 1999; Marrus et al., 2004; Pawlu et al., 2004).;Here I look at how Drosophila transcript abundance of the A and B-type subunits is affected during embryonic development and how a specific event, innervation, during embryonic development affects this abundance. After transcript production occurs, I investigate a method of post-transcriptional regulation of these A and B-type transcripts. I explore the regulation of these glutamate receptor subunit transcripts by microRNAs, with microRNA regulation being a possible method to modulate receptor subtype composition at the synapse through microRNA mediated transcript degradation.