DIACYLGLYCEROL KINASE THETA AT THE SYNAPSE: A ROLE FOR THE METABOLISM OF DAG IN SYNAPTIC VESICLE RECYCLING

diacylglycerol kinase;phosphatidic acid;diacylglycerol;synaptic vesicle recycling;endocytosis;exocytosis;Biochemistry

Goldschmidt, Hana LeahMachamer, Carolyn ;

Johns Hopkins University

关键词: diacylglycerol kinase;    phosphatidic acid;    diacylglycerol;    synaptic vesicle recycling;    endocytosis;    exocytosis;    Biochemistry;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/60552/GOLDSCHMIDT-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

In the mammalian nervous system, synaptic transmission relies on coordinated coupling of synaptic vesicle (SV) exocytosis and endocytosis. While much attention has focused on characterizing the proteins involved in SV recycling, the roles of membrane lipids and their metabolism remain poorly understood. Diacylglycerol, a major signaling lipid produced at synapses during synaptic transmission, is regulated by diacylglycerol kinase (DGK). Of the ten known mammalian DGK isoforms, DGKθ is one of the least studied DGK isoforms found in the brain with no known function to date. The goal of this study aimed to identify and characterize the function of DGKθ in the mammalian CNS. This thesis describes the first functional role for DGKθ in the mammalian central nervous system in facilitating recycling of presynaptic vesicles at excitatory synapses. Using an optical reporter, we found that acute and chronic deletion of DGKθ attenuated the recovery of SVs following neuronal stimulation. Rescue of recycling kinetics required DGKθ kinase activity. Our data establish a role for DGK catalytic activity and its byproduct, phosphatidic acid, at the presynaptic nerve terminal in facilitating SV recycling. Together these data suggest DGKθ supports synaptic transmission during periods of elevated neuronal activity.