Biochemical and Morphological Characterization of a Neurodevelopmental Disorder-Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2
Biochemical and Morphological Characterization of a Neurodevelopmental Disorder-Related Mono-ADP-Ribosylhydrolase, MACRO Domain Containing 2
复制标题
DOI：
10.1159/000492271
复制
发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Nagata, Koh-ichi
中科院分区：
文献类型：
--
作者：
Ito, Hidenori;Morishita, Rika;Nagata, Koh-ichi
macrodomain Containing 2 （MacroD2）是一种与神经发育障碍相关的单adp -核糖基水解酶。这种蛋白质在神经组织中的分子特征在很大程度上是未知的。在本研究中，我们制备了一种针对MacroD2的特异性抗体，并在小鼠脑发育过程中对该分子进行了表达和形态学分析。Western blotting结果显示，2个分子量分别为70和75 kDa的MacroD2亚型在胚胎期16.5 d开始表达，在出生后8 d达到最大水平，P30后逐渐减少。相比之下，其他分子量为110和140 kDa的同工异构体在胚胎到出生后的发育过程中逐渐增加。免疫组化分析显示，在P0和P7时，大鼠皮质II-V层神经元中存在较强的MacroD2表达，而在P30时，该蛋白的表达明显降低。免疫荧光分析显示，在未成熟的原代培养小鼠海马神经元中，MacroD2主要分布在体细胞中，少量分布在轴突和树突中。另一方面，在成熟海马神经元中，虽然在体细胞中检测到MacroD2，但它在树突中表现为点状分布，与突触标记物、synaptophysin和PSD95部分共定位。这些结果表明，在大脑发育过程中，MacroD2在中枢神经系统中表达并可能具有生理作用。（三）2018年凯格股份有限公司巴塞尔协议
MACRO Domain Containing 2 (MacroD2) is a neurodevelopmental disorder-related mono-ADP-ribosylhydrolase. Molecular features of this protein in neural tissues are largely unknown. In this study, we generated a specific antibody against MacroD2, and carried out expression and morphological analyses of the molecule during mouse brain development. In Western blotting, 2 MacroD2 isoforms with molecular masses of similar to 70 and similar to 75 kDa started to be expressed at embryonic day 16.5, reached the maximal level at postnatal day 8, and then gradually decreased through P30. In contrast, other isoforms with molecular masses of similar to 110 and similar to 140 kDa gradually increased during embryonic to postnatal development. In immunohistochemical analyses, MacroD2 was strongly detected in cortical neurons in layer II-V at P0 and P7, while the protein expression decreased significantly in the neurons at P30. Immunofluorescence analyses revealed that MacroD2 was mainly distributed in the soma and to a lesser extent in the axon and dendrite of immature primary cultured mouse hippocampal neurons. On the other hand, in the matured hippocampal neurons, while MacroD2 was detected in the soma, it displayed in dendrites a punctate distribution pattern with a partial colocalization with synaptic markers, synaptophysin, and PSD95. The obtained results indicate that MacroD2 is expressed and may have a physiological role in the central nervous system during brain development. (C) 2018 S. Karger AG. Basel