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Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs. These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems. In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses. In plants DGK mediated PA formation contributes to plant responses to environmental signals. Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential.

T cell receptor --- immunotherapy of cancer --- immune system --- synaptic transmission --- synaptic plasticity (LTP/LTD) --- cytotoxic T cells --- lipid signaling --- tolerance --- T cell receptor --- immunotherapy of cancer --- immune system --- synaptic transmission --- synaptic plasticity (LTP/LTD) --- cytotoxic T cells --- lipid signaling --- tolerance

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Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DG), catalyzing its conversion into phosphatidic acid (PA). This reaction attenuates membrane DG levels, limiting the localization/activation of signaling proteins that bind this lipid. Initially recognized as modulators of classical and novel PKC family members, the function of the DGK has further expanded with the identification of novel DG effectors including Ras Guanyl nucleotide-releasing proteins (RasGRP) and chimaerin Rac GTPases. The product of the DGK reaction, PA, is also a signaling lipid that mediates activation of multiple proteins including the mammalian target of rapamycin (mTOR). The DGK pathway thus modulates two lipids with important signaling properties that are also key intermediates in lipid metabolism and membrane trafficking. The DGK family in eukaryotes comprises 10 different members grouped into five different subfamilies characterized by the presence of particular regulatory motifs. These regions allow the different DGK isoforms to establish specific complexes and/or to be recruited to specific subcellular compartments. The subtle regulation of DG and PA catalyzed byspecific DGKs is sensed by a restricted set of molecules, providing the means for spatio-temporal regulation of signals in highly specialized cell systems. In the recent years, multiple studies have unveiled the functions of specific isoforms, their mechanisms of regulation and their participation in different pathways leading to and from DG and PA. Animal models have greatly helped to understand the specialized contribution of DGK mediated signals, particularly in the immune and central nervous systems. Mice deficient for individual DGK isoforms show defects in T and B cell functions, dendritic spine maintenance, osteoclast and mechanical-induced skeletal muscle formation. Studies in flies and worms link DGK mediated DAG metabolism with mTOR- mediated regulation of lifespan and stress responses. In plants DGK mediated PA formation contributes to plant responses to environmental signals. Aberrant DGK function has been recently associated with pathological states, an expected consequence of the essential role of these enzymes in the regulation of multiple tissue and systemic functions. DGK mutations/deletions have been related to human diseases including diabetes, atypical hemolytic-uremic syndrome, Parkinson disease and bipolar disorders. On the contrary DGK upregulation emerges as a non-oncogenic addition of certain tumors and represents one of the main mechanism by which cancer evades the immune attack. As a result, the DGK field emerges an exciting new area of research with important therapeutic potential.

T cell receptor --- immunotherapy of cancer --- immune system --- synaptic transmission --- synaptic plasticity (LTP/LTD) --- cytotoxic T cells --- lipid signaling --- tolerance

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Development of new imaging technologies in recent years has transformed neuroscience in profound ways. Following on the heels of the revolution based on the Green Fluorescent Protein, refined genetically-encoded fluorescent reporters and genetic targeting strategies now enable optical recording of synaptic transmission in defined neuronal populations at speeds approaching the enviable temporal resolution of electrophysiology. Super-resolution light microscopy permits observation of synapses and their molecular machinery at sub-diffraction resolution. At the ultrastructural level, automated forms of electron microscopy, improvements in specimen fixation methods, and recent efforts to correlate data from light and electron micrographs now make the reconstruction of functional neural circuits a reality. Finally, the use of optogenetic actuators, such as channelrhodopsins, allows precise temporal and spatial manipulation of neuronal activity and is revealing profound insights into the organization of neural circuits and their roles in behavior. This research topic highlights recent advances in both light and electron microscopy, with a specific focus on approaches that combine innovations from several different fields to obtain novel information about synapse structure and function. We are confident that this collection of articles - three original research papers, six reviews, one methods paper and one perspective article - will enable neuroscientists to achieve the next generation of experiments aimed at cracking the neural code.

connectomics --- super-resolution --- optogenetics --- Schizophrenia --- metabotropic glutamate receptors --- brain circuits --- functional imaging --- Electron microscopy --- calcium imaging --- Synaptic Transmission --- synaptic vesicle trafficking

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Neurotransmitters --- Neurotransmitter receptors --- Neurons --- Neuroglia --- Synaptic Transmission. --- Receptors, Neurotransmitter. --- Signal Transduction. --- Neurons. --- Neuroglia. --- Neurotransmitter receptors. --- neurotransmitters --- ion channels --- receptors --- neurodegeneration --- neuropharmacology --- hormone --- Chemical nerve transmitters --- Nerve transmitter substances --- Neural transmitters --- Neurohumors --- Neuroregulators --- Synaptic transmitters --- Transmitters, Chemical nerve --- Transmitters, Synaptic --- Neurochemistry --- Neural transmission --- Nerve Cells --- Cell, Nerve --- Cells, Nerve --- Nerve Cell --- Neuron --- Receptor Mediated Signal Transduction --- Signal Transduction Pathways --- Signal Transduction Systems --- Receptor-Mediated Signal Transduction --- Signal Pathways --- Pathway, Signal --- Pathway, Signal Transduction --- Pathways, Signal --- Pathways, Signal Transduction --- Receptor-Mediated Signal Transductions --- Signal Pathway --- Signal Transduction Pathway --- Signal Transduction System --- Signal Transduction, Receptor-Mediated --- Signal Transductions --- Signal Transductions, Receptor-Mediated --- System, Signal Transduction --- Systems, Signal Transduction --- Transduction, Signal --- Transductions, Signal --- Cell Communication --- Receptor-CD3 Complex, Antigen, T-Cell --- Receptor Cross-Talk --- Feedback, Physiological --- Gasotransmitters --- Neuromediator Receptor --- Neuromodulator Receptor --- Neuroregulator Receptor --- Neurotransmitter Receptor --- Receptors, Neuromediators --- Receptors, Neuromodulators --- Receptors, Neuroregulators --- Receptors, Neurotransmitters --- Neurohumor Receptors --- Neuromediator Receptors --- Neuromodulator Receptors --- Neuroregulator Receptors --- Receptors, Neurohumor --- Receptors, Synaptic --- Synaptic Receptors --- Neuromediators Receptors --- Neuromodulators Receptors --- Neuroregulators Receptors --- Neurotransmitter Receptors --- Neurotransmitters Receptors --- Receptor, Neuromediator --- Receptor, Neuromodulator --- Receptor, Neuroregulator --- Receptor, Neurotransmitter --- Receptors, Neuromediator --- Receptors, Neuromodulator --- Receptors, Neuroregulator --- Transmission, Neural --- Transmission, Synaptic --- Neural Transmission --- Neurotransmission --- Neural Conduction --- Synapses --- Glial cells --- Nerve tissue --- Nerves --- Nerve cells --- Neurocytes --- Cells --- Nervous system --- Receptors, Neurotransmitter --- Cell receptors --- Hormone receptors --- Neural receptors --- Cell Signaling --- Neurostransmitters --- Synaptic Receptor --- Receptor, Synaptic