Major and Classification
Majoring in Biopharmaceutical Sciences with a Minor in Cinematic Arts
Faculty Mentor
Dr. Dion K. Dickman – USC Dornsife College of Letters, Arts, and Sciences
Department
Mann School of Pharmacy and Biopharmaceutical Sciences
Research Gateway Project
Neto-Beta’s Role in the Recruitment of Glutamate Receptors in the Drosophila Neuromuscular Junction
Project Abstract
Synapses play a large role in communication in our bodies as they underlie cognition and behavior in the Central Nervous System (CNS). When changes occur, neurodevelopment disorders arise. In this junction, receptors such as ionotropic glutamate receptors (iGluRs) are present. These receptors are ligand-gated ion channels and are the primary mediators of communication in the CNS. When these are activated, glutamate – the most abundant neurotransmitter in the human brain – is released in the Neuromuscular Junction (NMJ) which releases signals to help with memory, cognition, and mood regulation. However, the mechanisms that bring these receptors to the postsynaptic surface to be activated are understudied. The Drosophila Melanogaster, more commonly known as the fruit fly, is a great genetic model for studying iGluRs due to their similarities in genetic sequencing compared to vertebrate organisms. Neto, an auxiliary protein that helps with the growth, connectivity, and guidance of glutamate receptors, is present in both fruit flies and vertebrates. It has been found that Neto is one of the mechanisms that engage with glutamate receptors in the NMJ, enabling further signals to be sent throughout the body that are necessary for survival. Neto has different isoforms – Alpha (α) and Beta (β) – that have different roles in the body due to differences in the genetic sequences. They have different domains in their C-terminus Tail that ultimately affect their function in the body. This can be seen with their varying C terminus tail size. Previous studies have shown that Neto-α is required for presynaptic increase and contributes to the functioning of neurotransmitter release, thus leading to the synapse organization and homeostasis in Drosophila Melanogaster, however, the role of Neto-β is still unclear. Here, we use CRISPR-Cas9 and electrophysiology on different Drosophila Melanogaster mutants – GluRIIA-PV3, GluRIIB-SP5, Neto-α Null, Neto-α Null lacking the IIA receptor, and Neto-β Null lacking the IIA receptor – to further understand the role of Neto in trafficking glutamate receptors both from and to the muscle membrane in the NMJ. We use the GluRIIA and GluRIIB mutants as a comparative model to figure out how Neto-α and Neto-β may interact with them differently. Our data proposes how the signal transduction changes at the Neuromuscular Junction when one of the Neto isoforms is not present during development. Without Neto-α, there is no change in mEPSP and quantal content signals in the GluRIIA mutant background, revealing that the Neto-α isoform has a larger role in trafficking glutamate receptors to the muscle membrane of the neuromuscular junction during homeostatic adaptation due to the difference in the C-Terminus Tail.