Molecular Mechanisms for Synapse Formation and Inter-Neuronal Connection

1. 我们已经证明，在钙粘蛋白功能的抑制下，树突棘异常延长，轴突-棘接触不稳定，突触前囊泡积聚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。我们对α n -连环蛋白突变小鼠海马神经元进行分析，发现其树突棘异常伸长，遗传学上证实了上述体外实验结果。我们还发现，在αN-catenin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对特定亚群的神经元前体的迁移也很重要。cadherin -11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大脑生理功能的调节。Cadherin-8敲除小鼠表现出另一种行为表型，目前正在详细研究中。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器，控制微管网络。这是钙粘蛋白和微管系统相互作用的首次展示。我们发现火烈鸟的7过跨膜钙粘蛋白在平面细胞的极性调控中起作用。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，它在视网膜外丛状层特异性表达。

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.