SynCAMs organize synapses through heterophilic adhesion
SynCAMs organize synapses through heterophilic adhesion
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DOI：
10.1523/jneurosci.2739-07.2007
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发表时间：
2007-11-14
影响因子：
5.3
通讯作者：
Biederer, Thomas
中科院分区：
文献类型：
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作者：
Fogel, Adam I.;Akins, Michael R.;Biederer, Thomas
突触是突触前和突触后并列的不对称细胞连接。跨突触黏附复合体被认为是组织发育中的突触的机制。然而，这些复合体的分子组成仍然不完全清楚，使我们无法理解跨突触间隙的粘连如何引导突触发育。在这里，我们定义了两个免疫球蛋白超家族成员，SynCAM1和2，它们在发育中的大脑中的神经元中表达，并定位于兴奋性和抑制性突触。它们发挥细胞黏附分子的作用，通过突触间隙相互组装成一个特定的、跨突触的SynCAM1/2复合体。此外，SynCAM 1和2促进功能性突触，因为它们增加了活跃的突触前终末的数量，并增强了兴奋性神经传递。SynCAM 1和2的相互作用受到糖基化的影响，表明这种黏附复合体受到翻译后修饰的调节。SynCAM 1/2复合体是该蛋白家族高度确定的黏附模式的代表，其四个成员在神经元中以不同的表达谱表达。SynCAM 1、2和3都可以结合自己，但优先组装成特定的异亲复合体，如突触SynCAM 1/2相互作用所示，第二个复合体由SynCAM 3和4组成。我们的结果将SynCAM蛋白质定义为新型跨突触黏附复合体的组成部分，这些复合体建立不对称相互作用，SynCAM蛋白参与突触的组织和功能。
Synapses are asymmetric cell junctions with precisely juxtaposed presynaptic and postsynaptic sides. Transsynaptic adhesion complexes are thought to organize developing synapses. The molecular composition of these complexes, however, remains incompletely understood, precluding us from understanding how adhesion across the synaptic cleft guides synapse development. Here, we define two immunoglobulin superfamily members, SynCAM 1 and 2, that are expressed in neurons in the developing brain and localize to excitatory and inhibitory synapses. They function as cell adhesion molecules and assemble with each other across the synaptic cleft into a specific, transsynaptic SynCAM 1/2 complex. Additionally, SynCAM 1 and 2 promote functional synapses as they increase the number of active presynaptic terminals and enhance excitatory neurotransmission. The interaction of SynCAM 1 and 2 is affected by glycosylation, indicating regulation of this adhesion complex by posttranslational modification. The SynCAM 1/2 complex is representative for the highly defined adhesive patterns of this protein family, the four members of which are expressed in neurons in divergent expression profiles. SynCAMs 1, 2, and 3 each can bind themselves, yet preferentially assemble into specific, heterophilic complexes as shown for the synaptic SynCAM 1/2 interaction and a second complex comprising SynCAM 3 and 4. Our results define SynCAM proteins as components of novel heterophilic transsynaptic adhesion complexes that set up asymmetric interactions, with SynCAM proteins contributing to synapse organization and function.