DGKι regulates presynaptic release during mGluR-dependent LTD.
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 DGKι. In addition, we establish that DGKι acts presynaptically, a function that contrasts with the known postsynaptic function of DGKζ, a close relative of DGKι. Deficiency of DGKι in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKι-/- 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 DGKι-/- synapses. These results suggest that DGKι requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.
Department of Biological Sciences, National Creative Research Initiative Center for Synaptogenesis, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Jinhee
J
Yang
Jinsoo
J
Seo
Ramya
R
Nair
Seungnam
S
Han
Seil
S
Jang
Karam
K
Kim
Kihoon
K
Han
Sang Kyoo
SK
Paik
Jeonghoon
J
Choi
Seunghoon
S
Lee
Yong Chul
YC
Bae
Matthew K
MK
Topham
Stephen M
SM
Prescott
Jeong-Seop
JS
Rhee
Se-Young
SY
Choi
Eunjoon
E
Kim
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D002478:Cells, Cultured; D019852:Diacylglycerol Kinase / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D016291:Dizocilpine Maleate; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C