DGKl regulates presynaptic release during mGluR-dependent LTD

Jinhee Yang; Jinsoo Seo; Ramya Nair; Seungnam Han; Seil Jang; Karam Kim; Kihoon Han; Sang Kyoo Paik; Jeonghoon Choi; Seunghoon Lee; Yong Chul Bae; Matthew K. Topham; Stephen M. Prescott; Jeong Seop Rhee; Se Young Choi; Eunjoon Kim

doi:10.1038/emboj.2010.286

DGKl regulates presynaptic release during mGluR-dependent LTD

Jinhee Yang, Jinsoo Seo, Ramya Nair, Seungnam Han, Seil Jang, Karam Kim, Kihoon Han, Sang Kyoo Paik, Jeonghoon Choi, Seunghoon Lee, Yong Chul Bae, Matthew K. Topham, Stephen M. Prescott, Jeong Seop Rhee, Se Young Choi, Eunjoon Kim

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

Abstract

Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKl. In addition, we establish that DGKl acts presynaptically, a function that contrasts with the known postsynaptic function of DGKl, a close relative of DGKl. Deficiency of DGKl in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKl^-/- synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (∼2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKl^-/- synapses. These results suggest that DGKl requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.

Original language	English
Pages (from-to)	165-180
Number of pages	16
Journal	EMBO Journal
Volume	30
Issue number	1
DOIs	https://doi.org/10.1038/emboj.2010.286
Publication status	Published - 2011 Jan 5
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
General Biochemistry,Genetics and Molecular Biology
General Immunology and Microbiology

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10.1038/emboj.2010.286

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title = "DGKl regulates presynaptic release during mGluR-dependent LTD",

abstract = "Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKl. In addition, we establish that DGKl acts presynaptically, a function that contrasts with the known postsynaptic function of DGKl, a close relative of DGKl. Deficiency of DGKl in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKl-/- synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (∼2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKl-/- synapses. These results suggest that DGKl requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.",

author = "Jinhee Yang and Jinsoo Seo and Ramya Nair and Seungnam Han and Seil Jang and Karam Kim and Kihoon Han and Paik, {Sang Kyoo} and Jeonghoon Choi and Seunghoon Lee and Bae, {Yong Chul} and Topham, {Matthew K.} and Prescott, {Stephen M.} and Rhee, {Jeong Seop} and Choi, {Se Young} and Eunjoon Kim",

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AU - Yang, Jinhee

AU - Seo, Jinsoo

AU - Nair, Ramya

AU - Han, Seungnam

AU - Jang, Seil

AU - Kim, Karam

AU - Han, Kihoon

AU - Paik, Sang Kyoo

AU - Choi, Jeonghoon

AU - Lee, Seunghoon

AU - Bae, Yong Chul

AU - Topham, Matthew K.

AU - Prescott, Stephen M.

AU - Rhee, Jeong Seop

AU - Choi, Se Young

AU - Kim, Eunjoon

PY - 2011/1/5

Y1 - 2011/1/5

N2 - Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKl. In addition, we establish that DGKl acts presynaptically, a function that contrasts with the known postsynaptic function of DGKl, a close relative of DGKl. Deficiency of DGKl in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKl-/- synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (∼2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKl-/- synapses. These results suggest that DGKl requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.

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DGKl regulates presynaptic release during mGluR-dependent LTD

Abstract

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