Expression of Neurexin, Neuroligin, and Their Cytoplasmic Binding Partners in the Pancreatic β-Cells and the Involvement of Neuroligin in Insulin Secretion
Expression of Neurexin, Neuroligin, and Their Cytoplasmic Binding Partners in the Pancreatic β-Cells and the Involvement of Neuroligin in Insulin Secretion
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DOI：
10.1210/en.2008-0274
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发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Chessler, Steven D.
中科院分区：
文献类型：
--
作者：
Suckow, Arthur T.;Comoletti, Davide;Chessler, Steven D.
β-细胞胞吐机制的组成与神经元突触的组成非常相似，并且β-细胞和神经元的发育途径基本上重叠。β细胞分泌γ-氨基丁酸，并表达蛋白质，在大脑中，这些蛋白质是抑制性突触的特异性标志物。最近，神经元共培养实验已经确定了三个家庭的突触细胞表面分子（neurexins，neuroligins，和SynCAM），驱动突触形成在体外和控制分化的新生突触成兴奋性或抑制性完全成熟的神经末梢。β细胞的抑制性突触样特征使我们假设这些突触诱导粘附分子家族的成员将在β细胞中表达，并且表达模式与神经元抑制性突触发生相关。在这里，我们描述了神经连接素，neurexins和SynCAM的β细胞表达，并表明神经连接素的表达影响INS-1 β细胞和大鼠胰岛细胞的胰岛素分泌。我们的研究结果表明，neuroligins和neurexins表达的中枢神经系统外，并帮助赋予抑制性突触样表型的β细胞表面。类似于它们在突触神经传递中的作用，neurexin-neuroligin相互作用可能在膜下胰岛素分泌装置的形成中发挥作用。（内分泌学149：6006-6017，2008）
The composition of the beta-cell exocytic machinery is very similar to that of neuronal synapses, and the developmental pathway of beta-cells and neurons substantially overlap. beta-Cells secrete gamma-aminobutyric acid and express proteins that, in the brain, are specific markers of inhibitory synapses. Recently, neuronal coculture experiments have identified three families of synaptic cell-surface molecules (neurexins, neuroligins, and SynCAM) that drive synapse formation in vitro and that control the differentiation of nascent synapses into either excitatory or inhibitory fully mature nerve terminals. The inhibitory synapse-like character of the beta-cells led us to hypothesize that members of these families of synapse-inducing adhesion molecules would be expressed in beta-cells and that the pattern of expression would resemble that associated with neuronal inhibitory synaptogenesis. Here, we describe beta-cell expression of the neuroligins, neurexins, and SynCAM, and show that neuroligin expression affects insulin secretion in INS-1 beta-cells and rat islet cells. Our findings demonstrate that neuroligins and neurexins are expressed outside the central nervous system and help confer an inhibitory synaptic-like phenotype onto the beta-cell surface. Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus. (Endocrinology 149: 6006-6017, 2008)