Molecular Mechanisms for Synapse Formation and Inter-Neuronal Connection

突触形成和神经元间连接的分子机制

• 批准号: 10102006
• 负责人: TAKEICHI Masatoshi
• 金额: $ 231.17万
• 依托单位: RIKEN (2002)Kyoto University (1998-2001)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10102006/
• 关键词: cadherin; catenin; synapse; neuron; hippocampus; cell adhesion; cerebellum; Purkinje cell; 神経回路; プルチンエ細胞; シナプシン; PSD-95; 網膜; 脳; LTP; p120

1. We have shown that under the suppression of cadherin function, dendritic spines abnormally elongate, axon-spine contacts are destabilized, and presynaptic vesicle accumulation and postsynaptic density protein organization are impaired. These findings provide the first compelling evidence for the important role of cadherin in synapse formation and maintenance2. We analyzed hippocampal neurons collected from αN-catenin mutant mice, and found that their dendritic spines abnormally elongated, genetically confirming the above in vitro results. We also found that, in the cerebellum of αN-catenin knockout mice, Purkinje cell migration is partly blocked, suggesting that this catenin is also important for the migration of particular subsets of neuronal precursors.3. Cadherin-11 knockout mice showed aberrant emotional behavior, such as reduced anxiety, suggesting that this cadherin is involved in the regulation of physiological brain functions. Cadherin-8 knockout mice show another behavioral phenotypes, which are under detailed investigation.4. We found that p120-catenin has the activity to bind cytoplasmic microtubules, suggesting that p120-catenin functions as a linker between microtubules and cell-cell junctions, controlling microtubule networks. This is the first demonstration for the interactions of the cadherin and microtubule systems.5. We discovered that the seven-passed transmembrane cadherin Flamingo plays a role in the regulation of planer cellular polarity.6. We identified a unique cadherin, present in both vertebrates and invertebrates, and in the former, it is specifically expressed in the outerplexiform layer of retina.

1.我们已经表明，在钙粘蛋白功能的抑制下，树突棘异常伸长，轴突棘接触不稳定，突触前囊泡积累和突触后密度蛋白组织受损。这些发现为钙粘蛋白在突触形成和维持中的重要作用提供了第一个令人信服的证据2。我们分析了从αN-catenin突变小鼠收集的海马神经元，发现它们的树突棘异常伸长，从遗传学上证实了上述体外结果。我们还发现，在αN-catenin基因敲除小鼠的小脑中，浦肯野细胞的迁移被部分阻断，这表明该catenin对特定神经元受体亚群的迁移也很重要. Cadherin-11基因敲除小鼠表现出异常的情绪行为，如焦虑减少，这表明这种钙粘蛋白参与了生理大脑功能的调节。Cadherin-8基因敲除小鼠表现出另一种行为表型，正在详细研究中.我们发现p120-catenin具有结合细胞质微管的活性，这表明p120-catenin作为微管和细胞-细胞连接之间的连接物起作用，控制微管网络。这是钙粘蛋白和微管系统相互作用的第一次证明.我们发现七次跨膜钙粘蛋白Flamingo在调节细胞平面极性中起作用。我们发现了一种独特的钙粘蛋白，存在于脊椎动物和无脊椎动物中，在前者中，它特异性地表达于视网膜的外网状层。