Functional analysis for signal transducsion via GPI-anchord neural cell adhesion molecules of contactin subgroup

接触素亚群GPI锚定神经细胞粘附分子信号转导的功能分析

• 批准号: 15500275
• 负责人: TAKEDA Yasuo
• 金额: $ 1.98万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500275/
• 关键词: neural cell adhesion molecule; contactin; NB-3; synapse; PSD-95; contactin associated protein; two-hybrid system; carboxypeptidase E; Two-Hybrid System; ミエリン; PDZ; GPI-アンカー型

Contactin subgroup molecules including contactin, TAG-1, NB-2, NB-3, BIG-1 and BIG-2 are GPI-anchored neural adhesion molecules belonged in immunoglobulin-superfamily(IGSF). A GPI-anchored molecule is known to attribute to detergent insoluble low-density fractions (lipid rafts) in which many signal transducing molecules are co-localized. In this study, I have investigated the functions of these molecules on the formation of brain organization and higher brain functions, especially focusing on signal transduction via synaptic transmission. Results were as follows.1)Contactin and NB-3 as well as contactin associated protein (Caspr 1) which is cis-interacted with contactin on the same side of plasma membrane were distributed in lipid raft fraction derived from synaptosome (postsynaptic density, PSD) of rat cerebral cortex.2)PSD-95 that is one of folding protein specifically localized in PSD was immunoprecipitated with both contactin and NB-3. And Caspr1 was detected in the precipitants with contactin, but not in that with NB-3.3)Total amount of proteins co-localized in the PSD derived from 30 month-old rat cortical synaptosome was less than that in PSD from 6 month-old. In contrast, cholesterol was much more contained in old PSD compared from young adult PSD. I have currently analyzed what kind of proteins were fluctuated by aging in cortical PSD fraction.4)Caspr2 and 4 belonging to the Caspr family were also localized in lipid raft. Analysis by East two-hybrid system, some interesting proteins were found to interact with the intracellular portion of either Caspr2 and 4. I have currently characterizing those proteins.These results suggested that contactin and NB-3 may cis-interact with caspr family and possibly involve in the postsynaptic functions.

Contactin亚类分子包括Contactin、TAG-1、NB-2、NB-3、BIG-1和BIG-2，它们是免疫球蛋白超家族（IGSF）中的GPI锚定的神经粘附分子。已知GPI锚定分子归因于去污剂不溶性低密度级分（脂筏），其中许多信号转导分子共定位。在这项研究中，我研究了这些分子对脑组织形成和高级脑功能的作用，特别是通过突触传递的信号转导。结果表明：1）Contactin和NB-3以及与Contactin在质膜同侧发生顺式相互作用的Contactin相关蛋白（Caspr 1）分布于大鼠大脑皮层突触体（postsynaptic density，PSD）的脂筏部分; 2）PSD-95是一种特异性定位于PSD的折叠蛋白。3）30月龄大鼠皮质突触体的PSD共定位蛋白总量少于6月龄大鼠PSD。相比之下，老年PSD中的胆固醇含量比青年PSD高得多。4）属于Caspr家族的Caspr 2和4也定位于脂筏中。通过East双杂交系统分析，发现一些有趣的蛋白质与Caspr 2和4的胞内部分相互作用。这些结果表明，contactin和NB-3可能与caspase家族发生顺式相互作用，并可能参与突触后功能。

项目成果

Developmental regulation of notochord-derived repulsion for dorsal root ganglion axons

• DOI: 10.1016/j.mcn.2003.10.005
• 发表时间: 2004-02-01
• 期刊: MOLECULAR AND CELLULAR NEUROSCIENCE
• 影响因子: 3.5
• 作者: Masuda, T;Fukamauchi, F;Shiga, T
• 通讯作者: Shiga, T

F3/Contactin acts as a functional for Notch during oligodendrocyte maturation.

F3/Contactin 在少突胶质细胞成熟过程中充当 Notch 的功能。

• 发表时间: 2003
• 期刊: CELL 115
• 作者: Hu;Q.-D.;Takeda;Y.;Xiao;Z;-C.et al.
• 通讯作者: -C.et al.

Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2

• DOI: 10.1046/j.1460-9568.2003.02514.x
• 发表时间: 2003-03-01
• 期刊: EUROPEAN JOURNAL OF NEUROSCIENCE
• 影响因子: 3.4
• 作者: Li, H;Takeda, Y;Watanabe, K
• 通讯作者: Watanabe, K

Antidepressants

• DOI: 10.1007/978-1-59259-474-0
• 发表时间: 1997
• 期刊: Reactions Weekly
• 作者: Rudolph E. Tanzi;Maarten E. A. Reith;Paul R. Sanberg;Klaus-Peter Ossenkopp;Martin Kavaliers;Linda M. Pullan;Antonia Vernadakis;Phyllis M. Gootman;Ivor E. Dreosti;P. Skolnick

Narcotics

毒品

• 发表时间: 2004
• 期刊: Illustrated Pharmacology, 2^<nd> Edition
• 作者: Takeda;Y.;Yamada;K.et al.
• 通讯作者: K.et al.