An extracellular network of Arabidopsis leucine-rich repeat receptor kinases

The cells of multicellular organisms (多细胞生物) receive extracellular signals using surface receptors (表面受体). The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability (易处理). In plants, the discovery of ECD interactions is complicated (使复杂化) by the massive expansion of receptor families, which creates tremendous potential for changeover (转变) in receptor interactions. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs; 富含亮氨酸重复受体激酶), which function in the sensing (感觉) of microorganisms, cell expansion, stomata development (气孔发育) and stem-cell maintenance. Although the principles that govern LRR-RK signalling activation are emerging, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay, and produced an LRR-based cell surface interaction network (CSILRR) that consists of 567 interactions. To demonstrate the power of CSILRR for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSILRR operates as a unified (统一的) regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant (异常的) signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.

多细胞生物的细胞会使用细胞表面受体接受胞外信号。细胞表面受体的胞外结构域作为互作介质，是受体激活的调控元件。因为胞外结构域在生化上难以处理的特性，理解胞外结构域之间的互作如何产生信号转导受体复合物十分具有挑战性。在植物中，鉴定胞外结构域之间的互作会变得更加复杂，因为植物的受体家族发生过多次扩张，创造了无数的潜在受体互作变化。在拟南芥中最大的一个受体家族含有225个进化上相关的富含亮氨酸重复受体激酶LRR-RKs，这些受体的作用是感知微生物、细胞扩张、气孔发育及干细胞维持。尽管关于LRR-RK信号激活的知识体系正在形成，然而这些蛋白家族系统水平的运作仍然未知。本文利用一个高敏的高通量蛋白互作检测试验调查了近四万个潜在的胞外结构域互作，成功构建了一个基于LRR的细胞表面互作网络CSILRR，共含567个互作事件。为鉴定CSILRR对于检测生物相关互作的作用，作者预测并验证了之前未知的LRR-RKs在植物发育及免疫方面的功能。另外，本文显示CSILRR作为统一的调控网络进行运转，LRR-RKs对于总的网络结构是至关重要的，以保证受体几个网络步骤信号转导功能的正常。因此，植物的LRR-RK网络演化以处理胞外信号使得响应保持平衡。

个人简介：2001年，法国巴黎第六大学，学士；2002年，巴黎第十一大学，硕士；2005年，美国北卡罗来纳大学教堂山分校，博士。

doi: 10.1038/nature25184