Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons.
Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons.
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DOI：
10.1186/1471-2202-10-99
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发表时间：
2009-08-19
期刊：
影响因子：
2.4
通讯作者：
Goto K
中科院分区：
文献类型：
--
作者：
Hozumi Y;Watanabe M;Otani K;Goto K
二酰基甘油激酶（DGK）是将二酰基甘油磷酸化为磷脂酸的酶，并且包括具有不同性质的多种同工酶。在DGKs中，在纹状体中强烈检测到DGKβ的mRNA信号，并且在GenBank中注释了来源于人DGKβ基因座的转录物之一，其在双相情感障碍患者中差异表达。最近，我们报道DGKβ在纹状体的中型棘神经元中表达，并且高度集中在树突棘的突触周。然而，DGKβ如何在细胞水平上参与神经元的病理生理作用仍然是难以捉摸的。本研究利用转染的海马神经元研究DGKβ在海马中的表达和亚细胞定位及其功能意义。DGKβ不仅在投射神经元中表达，而且在中间神经元中也表达，并且集中在非对称突触的突触周部位。在转染的海马神经元中，野生型DGKβ的过表达在体外（DIV）7 d促进树突生长，在14 DIV促进棘成熟，尽管其激酶死亡突变体没有影响。在海马中，DGKβ在投射神经元和中间神经元中表达，并在不对称突触中的树突棘的突触周处积累。转染实验表明DGKβ可能通过其激酶活性参与树突生长和棘发生的分子机制。
Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to phosphatidic acid and comprises multiple isozymes of distinct properties. Of DGKs, mRNA signal for DGKβ is strongly detected in the striatum, and one of the transcripts derived from the human DGKβ locus is annotated in GenBank as being differentially expressed in bipolar disorder patients. Recently, we have reported that DGKβ is expressed in medium spiny neurons of the striatum and is highly concentrated at the perisynapse of dendritic spines. However, it remains elusive how DGKβ is implicated in pathophysiological role in neurons at the cellular level. In the present study, we investigated the expression and subcellular localization of DGKβ in the hippocampus, together with its functional implication using transfected hippocampal neurons. DGKβ is expressed not only in projection neurons but also in interneurons and is concentrated at perisynaptic sites of asymmetrical synapses. Overexpression of wild-type DGKβ promotes dendrite outgrowth at 7 d in vitro (DIV) and spine maturation at 14 DIV in transfected hippocampal neurons, although its kinase-dead mutant has no effect. In the hippocampus, DGKβ is expressed in both projection neurons and interneurons and is accumulated at the perisynapse of dendritic spines in asymmetrical synapses. Transfection experiments suggest that DGKβ may be involved in the molecular machineries of dendrite outgrowth and spinogenesis through its kinase activity.
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DOI：
10.1073/pnas.90.16.7598
发表时间：
1993-08-15
影响因子：
11.1
作者：
GOTO, K;KONDO, H
通讯作者：
KONDO, H
影响因子：
3.4
作者：
Hozumi, Yasukazu;Fukaya, Masahiro;Goto, Kaoru
通讯作者：
Goto, Kaoru
影响因子：
11
作者：
Hill, J. J.;Hashimoto, T.;Lewis, D. A.
通讯作者：
Lewis, D. A.
影响因子：
3.4
作者：
Hozumi, Y;Ito, T;Goto, K
通讯作者：
Goto, K
影响因子：
16.2
作者：
Hayashi, ML;Choi, SY;Tonegawa, S
通讯作者：
Tonegawa, S