title: DGKθ Catalytic Activity Is Required for Efficient Recycling of Presynaptic Vesicles at Excitatory Synapses.
abstract: Synaptic transmission relies on coordinated coupling of synaptic vesicle (SV) exocytosis and endocytosis. While much attention has focused on characterizing 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). Here, we report a role for DGKθ in the mammalian CNS in facilitating recycling of presynaptic vesicles at excitatory synapses. Using synaptophysin- and vGlut1-pHluorin optical reporters, 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 at the presynaptic nerve terminal in SV recycling. Altogether, these data suggest that DGKθ supports synaptic transmission during periods of elevated neuronal activity.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Hunterian 503, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Hana L
authors.initials: HL
authors.lastname: Goldschmidt
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Hunterian 503, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Becky
authors.initials: B
authors.lastname: Tu-Sekine
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Hunterian 1001, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Lenora
authors.initials: L
authors.lastname: Volk
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Victor
authors.initials: V
authors.lastname: Anggono
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Hunterian 1001, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: rhuganir@jhmi.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Hunterian 503, 725 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: draben@jhmi.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Raben
mesh_terms: D000818:Animals; D008322:Mammals; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*