A cell surface interaction network of neural leucine-rich repeat receptors.
A cell surface interaction network of neural leucine-rich repeat receptors.
复制标题
富含神经亮氨酸重复受体的细胞表面相互作用网络。
DOI：
10.1186/gb-2009-10-9-r99
复制
发表时间：
2009
期刊：
影响因子：
12.3
通讯作者：
Wright GJ
中科院分区：
文献类型：
--
作者：
Söllner C;Wright GJ
使用高度严格的相互作用测定 AVEXIS 揭示了斑马鱼细胞外神经受体相互作用的网络。脊椎动物神经系统内大量精确的细胞间连接只能部分地用相对较少的已知细胞外引导信号来解释。神经孤儿受体蛋白的大家族已经被鉴定出来，并且可能有助于这些识别过程，但由于鉴定膜嵌入蛋白的新型细胞外相互作用的技术困难，它们的配体仍然未知。为了识别新的神经识别信号，我们进行了大型系统性蛋白质相互作用筛选，使用能够检测 150 种含有富含亮氨酸重复序列和/或免疫球蛋白超家族结构域的斑马鱼受体蛋白胞外域之间低亲和力细胞外蛋白质相互作用的测定法。我们筛选了 7,592 个相互作用，构建了 34 个细胞表面受体-配体对的网络，其中包括 Lrrtms、Lrrns 和 Elfns 等孤儿受体亚家族，以及 Robos 和 Unc5b 等已知受体的新型配体。对涉及 Unc5b 和三个 Flrt 受体的子网络进行的定量生化分析揭示了受体结合强度的令人惊讶的定量变化。成对的时空基因表达模式揭示了发育中的神经系统内的动态神经受体识别图，为网络提供了生物支持并揭示了可能的功能。这种集成的相互作用和表达网络提供了新型神经识别途径的丰富来源，并强调了定量系统细胞外蛋白质相互作用筛选对于机械解释神经布线模式的重要性。
A network of Zebrafish extracellular neuroreceptor interactions are revealed using AVEXIS, a highly stringent interaction assay. The vast number of precise intercellular connections within vertebrate nervous systems is only partly explained by the comparatively few known extracellular guidance cues. Large families of neural orphan receptor proteins have been identified and are likely to contribute to these recognition processes but due to the technical difficulty in identifying novel extracellular interactions of membrane-embedded proteins, their ligands remain unknown. To identify novel neural recognition signals, we performed a large systematic protein interaction screen using an assay capable of detecting low affinity extracellular protein interactions between the ectodomains of 150 zebrafish receptor proteins containing leucine-rich-repeat and/or immunoglobulin superfamily domains. We screened 7,592 interactions to construct a network of 34 cell surface receptor-ligand pairs that included orphan receptor subfamilies such as the Lrrtms, Lrrns and Elfns but also novel ligands for known receptors such as Robos and Unc5b. A quantitative biochemical analysis of a subnetwork involving the Unc5b and three Flrt receptors revealed a surprising quantitative variation in receptor binding strengths. Paired spatiotemporal gene expression patterns revealed dynamic neural receptor recognition maps within the developing nervous system, providing biological support for the network and revealing likely functions. This integrated interaction and expression network provides a rich source of novel neural recognition pathways and highlights the importance of quantitative systematic extracellular protein interaction screens to mechanistically explain neural wiring patterns.
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影响因子：
64.5
作者：
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通讯作者：
Kidd, T
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作者：
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