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DGK iota regulates presynaptic release during mGluR-dependent LTD

Cited 33 time in Web of Science Cited 43 time in Scopus
Authors
Yang, Jinhee; Seo, Jinsoo; Nair, Ramya; Han, Seungnam; Kim, Karam; Paik, Sang Kyoo; Lee, Seunghoon; Topham, Matthew K.; Rhee, Jeong-Seop; Kim, Eunjoon; Choi, Se-Young; Prescott, Stephen M.; Bae, Yong Chul; Choi, Jeonghoon; Han, Kihoon; Jang, Seil
Issue Date
2011-01-05
Publisher
NATURE PUBLISHING GROUP
Citation
EMBO JOURNAL, Vol.30, No.1, pp.165-180
Keywords
diacylglycerol kinaselong-term depressionmetabotropic glutamate receptorsPSD-95phospholipase C
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 DGK iota. In addition, we establish that DGK iota acts presynaptically, a function that contrasts with the known postsynaptic function of DGK zeta, a close relative of DGK iota. Deficiency of DGK iota in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGK iota(-/-) synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mCluR-LTD) at neonatal (similar to 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 DGK iota(-/-) synapses. These results suggest that DGK iota requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD. The EMBO Journal (2011) 30, 165-180. doi:10.1038/emboj.2010.286; Published online 30 November 2010
ISSN
0261-4189
Language
English
URI
https://hdl.handle.net/10371/80553
DOI
https://doi.org/10.1038/emboj.2010.286
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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