%0 PDF %T The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of C. elegans. %A Monteiro, Michael. %D 2017-04-14T13:39:06.718Z %8 2017-04-14 %R http://localhost/files/m900p642f %X Abstract: Glutamate is the major excitatory neurotransmitter in the mammalian brain. Changes in the strength of glutamatergic synapses are thought to underlie learning and memory and to contribute to the pathology of numerous neurological diseases. The transport of glutamate receptors from the cell body to synapses contributes to the regulation of synaptic strength. We previously showed that cyclin-dependent kinase-5 (CDK-5) positively regulates the abundance of fluorescently-tagged GLR-1 glutamate receptors at synapses in the ventral nerve cord (VNC) of C. elegans. In this thesis I investigate the roles of novel regulators of GLR-1 abundance in the VNC. In Chapter 2, I generate genetic mutants that suppress the effects of cdk-5 overexpression on GLR-1 abundance at synapses to identify genes that regulate GLR-1 abundance in the VNC and that may function in the same cellular pathway as CDK-5. I identify a mutation in klp-4/KIF13, which encodes a kinesin-3 family motor as a strong suppressor of increased GLR-1 abundance in animals that overexpress cdk-5. In Chapter 3, I characterize the novel kinesin motor KLP-4 and its role in GLR-1 trafficking. I find that klp-4 mutants have decreased abundance of GLR-1 at synapses in the VNC. Time-lapse microscopy indicates that klp-4 and cdk-5 mutants exhibit decreased anterograde trafficking of GLR-1. I conduct genetic analyses on klp-4 mutants with loss and gain of function of cdk-5 and find that KLP-4 and CDK-5 function in the same pathway to regulate GLR-1 in the VNC. Interestingly, I find that loss of function of KLP-4 affects GLR-1 levels in the cell body differently than loss of function of CDK-5. GLR-1 abundance increases in cell bodies of cdk-5 mutants but is unchanged in klp-4 mutants. However, GLR-1 does accumulate in klp-4 mutant cell bodies if receptor degradation in the MVB/lysosome pathway is blocked, suggesting that in the absence of its KLP-4 motor, GLR-1 is degraded. Finally, in Chapter 4, I investigate potential mechanisms for control of KLP-4 activity and identify a microRNA family, mir-75/mir-79 and the kinesin-1 motor, unc-116/Kif5 as novel regulators of GLR-1 abundance in the VNC.; Thesis (Ph.D.)--Tufts University, 2013.; Submitted to the Dept. of Cellular & Molecular Physiology.; Advisor: Peter Juo.; Committee: Dan Jay, Laura Liscum, Brent Cochran, and Josh Kaplan.; Keywords: Physiology, Neurosciences, and Genetics. %[ 2022-10-11 %9 Text %~ Tufts Digital Library %W Institution