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Neural recognition molecules, NrCAM and Contactin, during development and aging.

发育和衰老过程中的神经识别分子 NrCAM 和 Contactin。

基本信息

批准号：
10832010
负责人：
HOSOYA Hiroko
金额：
$ 2.11万
依托单位：
Tokyo Metropolitan Institute of Gerontology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10832010/
关键词：
NrCAM contactin adhesion molecule splicing isoform Ig-superfamily Nr-CAM 糖鎖脳の発達接着分子

项目摘要

Various cell adhesion molecules participate in the cell recognition events not only during development, but also in adulthood and during aging. We have been studying the biological roles of contactin, a neural adhesion molecule in the immunoglobulin superfamily, in the aged brain. NrCAM is one of the immunoglobulin superfamily molecules, which is known to interact with contactin and TAG-1 of the contactin subgroup. In this study, we first investigated the expression of NrCAM during development and aging. In the Western blot analysis, we found two bands of 135-kDa and 130-kDa in the adult rat brain. The 130-kDa band was not detected until postnatal day 10, whereas the 135-kDa band was detected from embryo to adulthood. The cDNA that we found encoded a splicing isoform of NrCAM, which has additional 19 amino acid residues in the N-terminal region comparing with the NrCAM reported previously. In order to know whether the two bands on the Western blot analysis were the splicing isoforms or not, we performed RT-PCR. The developmental expression pattern of these two isoform transcripts detected by the RT-PCR conformed to the appearance of the two bands on the Western blot. These results have suggested that the two splicing isoforms play different roles form each other in the brain function. Next, we examined the interaction of NrCAM with the other contactin subgroup molecules. By the immunoprecipitation, it was demonstrated that NrCAM interacted with contactin and TAG-1 in the hippocampus, whereas the interaction with NB-3 of the another contactin subgroup molecule was not detected. Taken together, NrCAM do not interact with all the contactin subgroup molecules. The results obtained here will be of great use for understanding the roles of NrCAM during aging.

各种细胞粘附分子不仅在发育过程中参与细胞识别事件，而且在成年期和衰老过程中也参与细胞识别事件。我们一直在研究接触素（免疫球蛋白超家族中的一种神经粘附分子）在老年大脑中的生物学作用。 NrCAM 是免疫球蛋白超家族分子之一，已知与 contactin 和 contactin 亚组的 TAG-1 相互作用。在本研究中，我们首先研究了 NrCAM 在发育和衰老过程中的表达。在Western blot分析中，我们在成年大鼠大脑中发现了135-kDa和130-kDa两条带。直到出生后第 10 天才检测到 130 kDa 条带，而从胚胎到成年期均检测到 135 kDa 条带。我们发现的cDNA编码NrCAM的剪接同工型，与之前报道的NrCAM相比，其N末端区域多了19个氨基酸残基。为了了解Western blot分析中的两条带是否是剪接异构体，我们进行了RT-PCR。 RT-PCR检测到的这两种亚型转录物的发育表达模式与Western blot中两条带的出现一致。这些结果表明，两种剪接异构体在大脑功能中发挥着不同的作用。接下来，我们检查了 NrCAM 与其他 contactin 亚组分子的相互作用。免疫沉淀表明NrCAM与海马中的contactin和TAG-1相互作用，而未检测到与另一个contactin亚组分子NB-3的相互作用。总的来说，NrCAM 不与所有 contactin 亚组分子相互作用。这里获得的结果对于理解 NrCAM 在衰老过程中的作用非常有用。