Negative Feedback Mechanisms Regulating Neurotransmitter

Homeostasis is an indispensable phenomenon in the maintenance of living organisms. Genetic defects which disrupt negative feedback processes can impact homeostatic regulation, potentially resulting in disease. To uncover the molecular mechanisms governing these and other diseases potentially related to defective homeostasis, I used the Drosophila neuromuscular junction as a model system. I characterized two potential mechanisms that regulate homeostasis within the nervous system. First, in Drosophila larval motor neurons, ligand activation of Drosophila metabotropic glutamate receptor A (DmGiuRA) mediates a Phosphoinositide 3-kinase (PI3K)-dependent downregulation of neuronal activity, but the mechanism by which mGiuR activates PI3K remains incompletely understood. Here, I identified Ca2+/Calmodulin-dependant protein kinase II (CaMKII) and the Focal adhesion kinase (DFak) as critical intermediates in the DmGiuRA-dependent activation of PI3K at Drosophila motor nerve terminals. I found that transgene-induced CaMKII inhibition or the DFaf<CG1 null mutation each block the ability of glutamate application to activate PI3K in larval motor nerve terminals, whereas transgene-induced CaMKII activation increases P13K activity