Cadherin superfamily genes: functions, genomic organization, and neurologic diversity.
Cadherin superfamily genes: functions, genomic organization, and neurologic diversity.
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DOI：
10.1101/gad.14.10.1169
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发表时间：
2000-05
影响因子：
10.5
通讯作者：
T. Yagi;M. Takeichi
中科院分区：
文献类型：
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作者：
T. Yagi;M. Takeichi
为了回答中枢神经系统（CNS）的高度复杂功能是如何产生的问题，我们需要深入了解产生大量多样化神经元及其特定相互作用的分子机制。中枢神经系统中复杂和高度组织化的神经网络最终产生大脑功能，包括先天和后天行为。有趣的是，中枢神经系统与免疫系统部分相似，两者都是由有限的基因组信息产生的复杂，多样化和组织良好的网络。免疫系统通过种系重排和/或体细胞突变使免疫球蛋白超家族的T细胞受体（TCR）和B细胞受体（BCR）随机多样化，从而促进对大量外源抗原的识别。CNS的类似调节过程尚不清楚。然而，最近的研究钙粘蛋白超家族提供了宝贵的见解，在中枢神经系统的多样化和有组织的网络的产生。迄今为止，已经鉴定了大量的钙粘蛋白超家族基因，其中大多数似乎在CNS中表达。特别是，初级钙粘蛋白（经典钙粘蛋白）被鉴定为突触组分，并且已经提出了它们在神经元回路、突触连接形成和突触可塑性中的作用（Suzuki et al. 1997; Tang et al. 1998; Honjo et al. 2000; Manabe et al. 2000; Tanaka et al. 2000）。此外，发现一种新的钙粘蛋白Arcadlin的表达在活动依赖性突触可塑性过程中上调（Yamagata et al. 1999）。此外，钙粘蛋白超家族的一个亚家族，与酪氨酸激酶Fyn结合的CNR（钙粘蛋白相关神经元受体）蛋白定位于突触膜中（Kohmura等，1998）。包括CNR在内的至少三个原钙粘蛋白基因亚家族源自与BCR和TCR基因簇相似的不寻常的基因组组织（Wu和Maniatis 1999; Sugino等2000）。这些研究结果有有趣的影响，在中枢神经系统，这可能会提供进一步的洞察过程中引起不同物种和个体的脑功能分化，以及精神疾病的分子基础的复杂和有组织的网络神经元连接的基础上的分子事件。
To answer the question of how the highly sophisticated functions of the central nervous system (CNS) are born, we need to gain insight into the molecular mechanisms that generate an enormous number of diversified neurons and their specific interactions. The complex and highly organized neural networks in the CNS ultimately generate brain function, including innate and acquired behavior. Interestingly, the CNS is in part similar to the immune system, both are produced as complex, diversified, and well-organized networks from limited genomic information. The immune system promotes the recognition of the enormous battery of foreign antigens through the random diversification of T-cell receptors (TCR) and B-cell receptors (BCR) of the immunoglobulin superfamily by germ line rearrangement and/or somatic mutation. Analogous regulatory processes are not known for the CNS. However, recent studies of the cadherin superfamily have provided valuable insights into the generation of diversified and organized networks in the CNS. A large number of cadherin superfamily genes have been identified to date, and most of them seem to be expressed in the CNS. In particular, primary cadherins (classic cadherins) were identified as synaptic components, and roles for them in neuronal circuitry, synaptic junction formation, and synaptic plasticity have been suggested (Suzuki et al. 1997; Tang et al. 1998; Honjo et al. 2000; Manabe et al. 2000; Tanaka et al. 2000). In addition, the expression of a novel cadherin, Arcadlin, was found to be up-regulated during activity-dependent synaptic plasticity (Yamagata et al. 1999). Moreover, a subfamily of the cadherin superfamily, CNR (cadherin-related neuronal receptor) proteins bound to tyrosine kinase Fyn, is localized in synaptic membrane (Kohmura et al. 1998). At least three protocadherin gene subfamilies including the CNRs are derived from an unusual genomic organization similar to that of BCR and TCR gene clusters (Wu and Maniatis 1999; Sugino et al. 2000). These findings have interesting implications regarding the molecular events underlying the establishment of complex and organized networks of neuronal connections in the CNS, which may provide further insight into the processes giving rise to diverged brain functions in various species and individuals, as well as the molecular basis of psychociatic diseases.